AKAP7 (A-kinase anchoring protein 7, also called AKAP15 or AKAP18) encodes a family of PKA anchoring proteins produced by alternative splicing. This entry covers the two short isoforms, AKAP18alpha (AKAP15) and AKAP18beta, which are targeted to the plasma membrane by myristoylation of the N-terminal glycine and dual palmitoylation of two adjacent cysteines. The gene also produces longer, cytosolic gamma and delta isoforms that carry a central 2H phosphoesterase domain and have distinct functions; what follows concerns the short membrane forms. In polarised epithelial cells the alpha form goes to the lateral membrane and the beta form to the apical membrane. Both bind the dimerization/docking domain of the PKA type II regulatory subunit through a shared amphipathic helix, positioning PKA at the membrane. The best-characterised target is the L-type calcium channel: AKAP15 binds the C-terminus of the CaV1.1 and CaV1.2 alpha1 subunits through a leucine-zipper interaction, placing PKA where it phosphorylates the channel, and peptides that disrupt this interaction blunt voltage-dependent potentiation in skeletal muscle and beta-adrenergic regulation of the channel in ventricular myocytes. A mouse lacking all AKAP7 isoforms nonetheless shows normal beta-adrenergic responses in ventricular myocytes, so the gene's necessity for cardiac calcium-channel regulation in vivo is unresolved. AKAP15 also co-purifies with brain voltage-gated sodium channels, can confer cAMP sensitivity on the cardiac IKs potassium channel when co-expressed, and reduces epithelial sodium channel activity by a PKA-independent mechanism in oocytes. In the hippocampus, AKAP7 in dentate granule cells is required for cAMP-induced long-term potentiation at mossy fiber synapses and for pattern-separation behaviour.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001508 action potential | IDA PMID:11299204 AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1... | UNDECIDED | Summary: Action potential. The abstract reports voltage-clamp currents only; whether the full text contains action-potential data could not be checked. Reason: PMID:11299204 shows a real experimental result - [PMID:11299204 "coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes"] - but read its framing: the three AKAPs are interchangeable, the effect is attributed to PKA anchoring in general [PMID:11299204 "We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs"], and it is heterologous and modest [PMID:11299204 "However, in cells expressing an AKAP, the effects of cAMP stimulation on the I(Ks) amplitude remained modest compared with those previously reported in cardiac myocytes."]. So AKAP15/18 can confer cAMP regulation on the IKs channel when supplied, which is a property of being an AKAP, not evidence that AKAP7 is the anchor for IKs in myocytes. The curator read the full text and the result stands; it is kept, but marked non-core. This row needs more than the others. The abstract describes IKs currents in heterologous expression systems under voltage clamp and never mentions action potentials. The full text may contain action-potential recordings or modelling that justify the curator's IDA, but it could not be accessed (the publisher returns 403 and there is no PMC copy). Per the action definition, an annotation that cannot be checked against its publication is UNDECIDED rather than removed - the curator saw what I could not. Supporting Evidence: PMID:11299204 coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes |
| GO:0005886 plasma membrane | TAS PMID:10613906 Alternative splicing regulates the subcellular localization ... | ACCEPT | Summary: Plasma membrane. The defining location of the short isoforms this entry covers, set by N-terminal lipidation. Reason: Both isoforms in this entry are membrane-targeted [PMID:10613906 "The original AKAP18 (renamed AKAP18alpha) and AKAP18beta target the plasma membrane when expressed in HEK-293 cells, while AKAP18gamma is cytosolic."], through lipid modification of the N-terminus [PMID:9545239 "Membrane anchoring is mediated by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid-modified through myristoylation and dual palmitoylation, respectively."]. Note the scoping: the cytosolic gamma form is a separate UniProt entry, so this location holds for every product annotated here. Supporting Evidence: PMID:10613906 The original AKAP18 (renamed AKAP18alpha) and AKAP18beta target the plasma membrane when expressed in HEK-293 cells, while AKAP18gamma is cytosolic. PMID:9545239 Membrane anchoring is mediated by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid-modified through myristoylation and dual palmitoylation, respectively. |
| GO:0006811 monoatomic ion transport | TAS PMID:9545239 A novel lipid-anchored A-kinase Anchoring Protein facilitate... | MODIFY | Summary: Monoatomic ion transport. AKAP18 does not transport ions; it regulates a channel that does. Modified to the regulatory term. Reason: The participation test is the issue. An AKAP does none of the work of moving ions - the CaV1 channel does - but it does regulate that channel by anchoring PKA to it, directly and via a defined motif: [PMID:11733497 "Here we report that AKAP15 directly interacts with the C-terminal domain of the alpha(1) subunit of Ca(V)1.1 via a leucine zipper (LZ) motif."], and disrupting that interaction [PMID:11733497 "Disruption of the LZ interaction effectively inhibits voltage-dependent potentiation of L-type Ca(2+) channels in skeletal muscle cells."]. The same holds for cardiac CaV1.2 [PMID:14569017 "Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif."]. So the essence of this traceable author statement is sound but the role is conflated. GO:1901385 regulation of voltage-gated calcium channel activity states it correctly and names the mechanism: what anchored PKA modulates is the activity of a voltage-gated channel, shown as voltage-dependent potentiation. Direction-neutral deliberately. One caveat travels with it: in ventricular myocytes, knocking out every AKAP7 isoform did not impair beta-adrenergic regulation [PMID:23035250 "KO cardiomyocytes responded normally to adrenergic stimulation, as measured by whole-cell patch clamp or a fluorescent intracellular Ca(2+) indicator."], which conflicts with the peptide-disruption result. The regulatory capacity is established; its necessity in the heart is contested, and is recorded as a knowledge gap. Proposed replacements: regulation of voltage-gated calcium channel activity Supporting Evidence: PMID:11733497 Here we report that AKAP15 directly interacts with the C-terminal domain of the alpha(1) subunit of Ca(V)1.1 via a leucine zipper (LZ) motif. PMID:11733497 Disruption of the LZ interaction effectively inhibits voltage-dependent potentiation of L-type Ca(2+) channels in skeletal muscle cells. PMID:14569017 Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif. PMID:23035250 KO cardiomyocytes responded normally to adrenergic stimulation, as measured by whole-cell patch clamp or a fluorescent intracellular Ca(2+) indicator. file:genes/human/AKAP7/AKAP7-deep-research-affinage.md It anchors PKA to skeletal muscle L-type Ca2+ channels through a leucine-zipper interaction with the CaV1.1 alpha1 C-terminus |
| GO:0008104 intracellular protein localization | IC PMID:9545239 A novel lipid-anchored A-kinase Anchoring Protein facilitate... | MODIFY | Summary: Intracellular protein localization, inferred by the curator from AKAP18 targeting PKA to the membrane. Correct; the paper names the destination, for which GO has a precise child term. Reason: The cloning paper states where AKAP18 sends PKA [PMID:9545239 "targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel."], and how it gets there itself: [PMID:9545239 "Membrane anchoring is mediated by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid-modified through myristoylation and dual palmitoylation, respectively."]. GO:0072659 protein localization to plasma membrane is a descendant of GO:0008104 (checked via OLS ancestors) and states the destination. A refinement of the curator's own inference. Proposed replacements: protein localization to plasma membrane Supporting Evidence: PMID:9545239 targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel. PMID:9545239 Membrane anchoring is mediated by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid-modified through myristoylation and dual palmitoylation, respectively. |
| GO:0016324 apical plasma membrane | IDA PMID:10613906 Alternative splicing regulates the subcellular localization ... | ACCEPT | Summary: Apical plasma membrane - where the beta isoform goes in polarised epithelial cells. Reason: Directly observed: [PMID:10613906 "When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane."]. The two locations are isoform-specific - alpha to the lateral membrane, beta to the apical - and both isoforms belong to this entry, so the gene-product annotation is correct for each; the rows simply do not record which isoform was observed. Supporting Evidence: PMID:10613906 When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Apical plasma membrane from the UniProt SubCell vocabulary; same observation as the IDA row. Reason: Directly observed: [PMID:10613906 "When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane."]. The two locations are isoform-specific - alpha to the lateral membrane, beta to the apical - and both isoforms belong to this entry, so the gene-product annotation is correct for each; the rows simply do not record which isoform was observed. Supporting Evidence: PMID:10613906 When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane. |
| GO:0016328 lateral plasma membrane | IDA PMID:10613906 Alternative splicing regulates the subcellular localization ... | ACCEPT | Summary: Lateral plasma membrane - where the alpha isoform goes in polarised epithelial cells. Reason: Directly observed: [PMID:10613906 "When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane."]. The two locations are isoform-specific - alpha to the lateral membrane, beta to the apical - and both isoforms belong to this entry, so the gene-product annotation is correct for each; the rows simply do not record which isoform was observed. Supporting Evidence: PMID:10613906 When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane. |
| GO:0016328 lateral plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Lateral plasma membrane from the UniProt SubCell vocabulary; same observation as the IDA row. Reason: Directly observed: [PMID:10613906 "When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane."]. The two locations are isoform-specific - alpha to the lateral membrane, beta to the apical - and both isoforms belong to this entry, so the gene-product annotation is correct for each; the rows simply do not record which isoform was observed. Supporting Evidence: PMID:10613906 When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes, whereas AKAP18beta is accumulated at the apical membrane. |
| GO:0035556 intracellular signal transduction | TAS PMID:10613906 Alternative splicing regulates the subcellular localization ... | KEEP AS NON CORE | Summary: Intracellular signal transduction. True - an AKAP scaffolds cAMP-PKA signalling - but too general to inform. Kept as non-core. Reason: AKAPs participate in cAMP signalling by scaffolding it, which satisfies the participation test in the structural sense [PMID:9545239 "targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel."]. The term is correct and very broad; the informative statements about this gene are the RII binding and the channel anchoring, so this is retained as a true but non-core parent. None of AKAP1, AKAP5 or AKAP9 carries it either. Supporting Evidence: PMID:9545239 targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel. |
| GO:0051018 protein kinase A binding | IDA PMID:9545239 A novel lipid-anchored A-kinase Anchoring Protein facilitate... | MODIFY | Summary: PKA binding, from the cloning paper. Correct; refined to the specific regulatory-subunit term that the AKAP family and the mouse ortholog carry. Reason: AKAP7 binds the PKA regulatory subunit specifically, and the structural evidence is on this entry's own isoform [PMID:27102985 "Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA."]; all isoforms share the site [PMID:10613906 "The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains."]. GO:0034237 protein kinase A regulatory subunit binding is the direct, childless child of GO:0051018 that says exactly this. The comparator check is unusually clean: AKAP1, AKAP5 and AKAP9 all carry GO:0034237, including by IBA, and so does the mouse AKAP7 ortholog by IDA. Human AKAP7 is the outlier carrying only the parent, so this harmonises it rather than inventing anything. Proposed replacements: protein kinase A regulatory subunit binding Supporting Evidence: PMID:27102985 Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA. PMID:10613906 The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains. |
| GO:0051018 protein kinase A binding | IEA GO_REF:0000117 | MODIFY | Summary: PKA binding from ARBA. Same fact as the experimental rows; refined identically so the term carries one action. Reason: AKAP7 binds the PKA regulatory subunit specifically, and the structural evidence is on this entry's own isoform [PMID:27102985 "Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA."]; all isoforms share the site [PMID:10613906 "The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains."]. GO:0034237 protein kinase A regulatory subunit binding is the direct, childless child of GO:0051018 that says exactly this. The comparator check is unusually clean: AKAP1, AKAP5 and AKAP9 all carry GO:0034237, including by IBA, and so does the mouse AKAP7 ortholog by IDA. Human AKAP7 is the outlier carrying only the parent, so this harmonises it rather than inventing anything. Proposed replacements: protein kinase A regulatory subunit binding Supporting Evidence: PMID:27102985 Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA. |
| GO:0051018 protein kinase A binding | TAS PMID:10613906 Alternative splicing regulates the subcellular localization ... | MODIFY | Summary: PKA binding, as stated in the splicing paper. Refined identically to the IDA row. Reason: AKAP7 binds the PKA regulatory subunit specifically, and the structural evidence is on this entry's own isoform [PMID:27102985 "Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA."]; all isoforms share the site [PMID:10613906 "The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains."]. GO:0034237 protein kinase A regulatory subunit binding is the direct, childless child of GO:0051018 that says exactly this. The comparator check is unusually clean: AKAP1, AKAP5 and AKAP9 all carry GO:0034237, including by IBA, and so does the mouse AKAP7 ortholog by IDA. Human AKAP7 is the outlier carrying only the parent, so this harmonises it rather than inventing anything. Proposed replacements: protein kinase A regulatory subunit binding Supporting Evidence: PMID:10613906 The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains. PMID:27102985 Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA. |
| GO:0060306 regulation of membrane repolarization | IDA PMID:11299204 AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1... | KEEP AS NON CORE | Summary: Regulation of membrane repolarization, from the IKs reconstitution study. IKs is a repolarising current, so this follows from the current measurements; kept as non-core. Reason: PMID:11299204 shows a real experimental result - [PMID:11299204 "coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes"] - but read its framing: the three AKAPs are interchangeable, the effect is attributed to PKA anchoring in general [PMID:11299204 "We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs"], and it is heterologous and modest [PMID:11299204 "However, in cells expressing an AKAP, the effects of cAMP stimulation on the I(Ks) amplitude remained modest compared with those previously reported in cardiac myocytes."]. So AKAP15/18 can confer cAMP regulation on the IKs channel when supplied, which is a property of being an AKAP, not evidence that AKAP7 is the anchor for IKs in myocytes. The curator read the full text and the result stands; it is kept, but marked non-core. IKs is the slow delayed rectifier, a repolarising current, so regulation of repolarisation is a fair reading of the current data even though the abstract does not measure repolarisation directly. Supporting Evidence: PMID:11299204 coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes PMID:11299204 We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs |
| GO:0071320 cellular response to cAMP | IDA PMID:11299204 AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1... | KEEP AS NON CORE | Summary: Cellular response to cAMP, from the IKs reconstitution study. AKAP15/18 confers cAMP responsiveness on the channel in these cells; kept as non-core. Reason: PMID:11299204 shows a real experimental result - [PMID:11299204 "coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes"] - but read its framing: the three AKAPs are interchangeable, the effect is attributed to PKA anchoring in general [PMID:11299204 "We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs"], and it is heterologous and modest [PMID:11299204 "However, in cells expressing an AKAP, the effects of cAMP stimulation on the I(Ks) amplitude remained modest compared with those previously reported in cardiac myocytes."]. So AKAP15/18 can confer cAMP regulation on the IKs channel when supplied, which is a property of being an AKAP, not evidence that AKAP7 is the anchor for IKs in myocytes. The curator read the full text and the result stands; it is kept, but marked non-core. Why this survives the participation test that the ion-transport row fails: an AKAP moves no ions, so it does none of the work of ion transport, but the cAMP response here is PKA phosphorylating the channel, and AKAP15/18 contributes the positioning that step depends on - the scaffold case CLAUDE.md counts as participation. Non-core because the result is AKAP-nonspecific, not because the participation is absent. Supporting Evidence: PMID:11299204 coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes PMID:11299204 We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs |
| GO:1901381 positive regulation of potassium ion transmembrane transport | IDA PMID:11299204 AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1... | KEEP AS NON CORE | Summary: Positive regulation of potassium ion transmembrane transport, from the IKs reconstitution study. A genuine result, but AKAP-nonspecific and heterologous; kept as non-core. Reason: PMID:11299204 shows a real experimental result - [PMID:11299204 "coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes"] - but read its framing: the three AKAPs are interchangeable, the effect is attributed to PKA anchoring in general [PMID:11299204 "We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs"], and it is heterologous and modest [PMID:11299204 "However, in cells expressing an AKAP, the effects of cAMP stimulation on the I(Ks) amplitude remained modest compared with those previously reported in cardiac myocytes."]. So AKAP15/18 can confer cAMP regulation on the IKs channel when supplied, which is a property of being an AKAP, not evidence that AKAP7 is the anchor for IKs in myocytes. The curator read the full text and the result stands; it is kept, but marked non-core. Supporting Evidence: PMID:11299204 coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes PMID:11299204 We concluded that cAMP regulation of I(Ks) requires protein kinase A anchoring by AKAPs PMID:11299204 However, in cells expressing an AKAP, the effects of cAMP stimulation on the I(Ks) amplitude remained modest compared with those previously reported in cardiac myocytes. |
| GO:0035591 signaling adaptor activity | IPI PMID:14569017 Beta-adrenergic regulation requires direct anchoring of PKA ... | NEW | Summary: AKAP15 bridges PKA to CaV1 calcium channels - binding the RII subunit on one side and the channel's C-terminal leucine zipper on the other. That is signaling adaptor activity, the branch the AKAP family carries. Reason: Participation: AKAP15 itself makes both contacts. It binds PKA's regulatory subunit [PMID:27102985 "Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA."] and the channel, directly [PMID:14569017 "Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif."], co-purifying with it [PMID:14569017 "A kinase-anchoring protein 15 (AKAP15) coimmunoprecipitates with CaV1.2 channels"], and the same for skeletal CaV1.1 [PMID:11733497 "Here we report that AKAP15 directly interacts with the C-terminal domain of the alpha(1) subunit of Ca(V)1.1 via a leucine zipper (LZ) motif."]. The term is GO:0035591 signaling adaptor activity, two levels below the adaptor root (GO:0060090 > GO:0030674 protein-macromolecule adaptor > GO:0035591), because both clients are proteins and both sit in one cAMP-PKA pathway - the narrowing the sibling AKAP12 review makes for the same reason. Its definition names tethering signalling components to specific locations, which is what an AKAP does. Comparator: AKAP5 and AKAP9 carry the adaptor branch, by IBA among other codes, so PAINT places it on the AKAP lineage. Not an ancestor or descendant of GO:0034237, a binding term in another branch. Evidence code IPI; the partner recorded is rat CaV1.2 (P22002), because that is the channel the binding experiments used - recording a human accession would misstate what was tested. Supporting Evidence: PMID:14569017 Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif. PMID:14569017 A kinase-anchoring protein 15 (AKAP15) coimmunoprecipitates with CaV1.2 channels PMID:11733497 Here we report that AKAP15 directly interacts with the C-terminal domain of the alpha(1) subunit of Ca(V)1.1 via a leucine zipper (LZ) motif. PMID:27102985 Here, we elucidated the structure of an extended PKA-binding domain of AKAP18Ξ² bound to the D/D domain of the regulatory RIIΞ± subunits of PKA. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Do the AKAP15-disrupting peptides also displace PKA from other AKAPs at CaV1.2, which would reconcile them with the normal knockout phenotype?
Q: Should human AKAP7 carry the mossy-fiber synaptic terms that the mouse ortholog has by IDA and IMP?
Q: Is the PKA-independent suppression of ENaC by AKAP15 seen in epithelia, or only in oocytes? A single heterologous study is too thin to annotate.
Q: Which isoform mediates the mossy-fiber role? The conditional deletion removes all of them, and only the short isoforms are in this entry.
Experiment: Isoform-selective knockout of AKAP18alpha in cardiomyocytes, which separates its CaV1.2 role from compensation by the long isoforms.
Experiment: Test whether the CaV1.2 leucine-zipper disrupting peptides displace PKA anchored by AKAP5 or other AKAPs in myocytes.
Experiment: Rescue the dentate granule cell knockout with individual isoforms to assign the mossy-fiber LTP function.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)