Metro is a p55/MPP-family MAGUK scaffold that organizes perisynaptic protein complexes at Drosophila larval neuromuscular junctions. Through its L27 domains it links DlgS97 and DLin-7, stabilizing synaptic organization and controlling bouton formation and postsynaptic receptor-field size. Its guanylate-kinase-like domain does not establish enzymatic phosphate transfer.
Summary: The guanylate-kinase-like domain of this MAGUK scaffold does not by itself establish nucleotide or ATP binding. The gene-specific study establishes L27-mediated scaffold assembly but does not provide an accessible nucleotide-binding assay. Residual ligand binding and catalytic activity are distinct questions, so the binding assertion remains unresolved.
Reason: The guanylate-kinase-like domain of this MAGUK scaffold does not by itself establish nucleotide or ATP binding. The gene-specific study establishes L27-mediated scaffold assembly but does not provide an accessible nucleotide-binding assay. Residual ligand binding and catalytic activity are distinct questions, so the binding assertion remains unresolved.
Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7.
Summary: The guanylate-kinase-like domain of this MAGUK scaffold does not by itself establish nucleotide or ATP binding. The gene-specific study establishes L27-mediated scaffold assembly but does not provide an accessible nucleotide-binding assay. Residual ligand binding and catalytic activity are distinct questions, so the binding assertion remains unresolved.
Reason: The guanylate-kinase-like domain of this MAGUK scaffold does not by itself establish nucleotide or ATP binding. The gene-specific study establishes L27-mediated scaffold assembly but does not provide an accessible nucleotide-binding assay. Residual ligand binding and catalytic activity are distinct questions, so the binding assertion remains unresolved.
Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7.
Summary: Metro is a perisynaptic submembranous scaffold at larval neuromuscular junctions. Direct localization and its DlgS97–DLin-7 complex support this junctional membrane location independently of the automated annotation provenance.
Reason: Metro is a perisynaptic submembranous scaffold at larval neuromuscular junctions. Direct localization and its DlgS97–DLin-7 complex support this junctional membrane location independently of the automated annotation provenance.
Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7.
Summary: Metro is a perisynaptic submembranous scaffold at larval neuromuscular junctions. Direct localization and its DlgS97–DLin-7 complex support this junctional membrane location independently of the automated annotation provenance.
Reason: Metro is a perisynaptic submembranous scaffold at larval neuromuscular junctions. Direct localization and its DlgS97–DLin-7 complex support this junctional membrane location independently of the automated annotation provenance.
Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7.
GO:0008582 regulation of synaptic assembly at neuromuscular junction
IMP PMID:20427642 A perisynaptic ménage à trois between Dlg, DLin-7, and Metro...
ACCEPT
Summary: Metro stabilizes a perisynaptic DlgS97–DLin-7 complex and is required for normal bouton formation and neuromuscular-junction expansion, directly supporting synapse organization as its core biological role.
Reason: Metro stabilizes a perisynaptic DlgS97–DLin-7 complex and is required for normal bouton formation and neuromuscular-junction expansion, directly supporting synapse organization as its core biological role.
In a remarkably interdependent manner, Metro and DLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons.
Summary: The exact Metro guanylate-kinase-like domain carries the scaffold-associated Ser-to-Pro change at the GMP-recognition site (Pro422), His488 at the position of catalytic-enzyme Asp101, and substantial ATP-loop remodeling. Independent alignments recover the known active-enzyme and MAGUK controls. Together with primary biochemical and structural evidence for repurposing of MPP/MAGUK GUK domains and the directly demonstrated Metro scaffold function, this refutes electronic transfer of conventional kinase/transferase activity. It does not imply complete loss of nucleotide binding.
Reason: The exact Metro guanylate-kinase-like domain carries the scaffold-associated Ser-to-Pro change at the GMP-recognition site (Pro422), His488 at the position of catalytic-enzyme Asp101, and substantial ATP-loop remodeling. Independent alignments recover the known active-enzyme and MAGUK controls. Together with primary biochemical and structural evidence for repurposing of MPP/MAGUK GUK domains and the directly demonstrated Metro scaffold function, this refutes electronic transfer of conventional kinase/transferase activity. It does not imply complete loss of nucleotide binding.
Supporting Evidence:
file:DROME/metro/metro-bioinformatics/RESULTS.md
The complete target segment corresponding to yeast residues 9–16 is **GAPGVGRN** (Metro396–403), compared with **GPSGTGKS** in yeast.
file:DROME/metro/metro-bioinformatics/RESULTS.md
Together with the observed pocket substitutions, it supports rejecting the electronic catalytic transfer.
Summary: The exact Metro guanylate-kinase-like domain carries the scaffold-associated Ser-to-Pro change at the GMP-recognition site (Pro422), His488 at the position of catalytic-enzyme Asp101, and substantial ATP-loop remodeling. Independent alignments recover the known active-enzyme and MAGUK controls. Together with primary biochemical and structural evidence for repurposing of MPP/MAGUK GUK domains and the directly demonstrated Metro scaffold function, this refutes electronic transfer of conventional kinase/transferase activity. It does not imply complete loss of nucleotide binding.
Reason: The exact Metro guanylate-kinase-like domain carries the scaffold-associated Ser-to-Pro change at the GMP-recognition site (Pro422), His488 at the position of catalytic-enzyme Asp101, and substantial ATP-loop remodeling. Independent alignments recover the known active-enzyme and MAGUK controls. Together with primary biochemical and structural evidence for repurposing of MPP/MAGUK GUK domains and the directly demonstrated Metro scaffold function, this refutes electronic transfer of conventional kinase/transferase activity. It does not imply complete loss of nucleotide binding.
Supporting Evidence:
file:DROME/metro/metro-bioinformatics/RESULTS.md
The complete target segment corresponding to yeast residues 9–16 is **GAPGVGRN** (Metro396–403), compared with **GPSGTGKS** in yeast.
file:DROME/metro/metro-bioinformatics/RESULTS.md
Together with the observed pocket substitutions, it supports rejecting the electronic catalytic transfer.
Summary: Metro is a perisynaptic submembranous scaffold at larval neuromuscular junctions. Direct localization and its DlgS97–DLin-7 complex support this junctional membrane location independently of the automated annotation provenance.
Reason: Metro is a perisynaptic submembranous scaffold at larval neuromuscular junctions. Direct localization and its DlgS97–DLin-7 complex support this junctional membrane location independently of the automated annotation provenance.
Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7.
IDA PMID:20427642 A perisynaptic ménage à trois between Dlg, DLin-7, and Metro...
ACCEPT
Summary: The full primary article explicitly localizes Metro to the subsynaptic reticulum by immunofluorescence (Figure 2G), supporting the existing gene-level IDA annotation. The predominant muscle isoform studied was Metro-B (556 residues); the selected isoform A retains the same L27/PDZ/SH3/GUK architecture, so the broad scaffold function is transferable without asserting isoform-specific localization measurements.
Reason: The full primary article explicitly localizes Metro to the subsynaptic reticulum by immunofluorescence (Figure 2G), supporting the existing gene-level IDA annotation. The predominant muscle isoform studied was Metro-B (556 residues); the selected isoform A retains the same L27/PDZ/SH3/GUK architecture, so the broad scaffold function is transferable without asserting isoform-specific localization measurements.
Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7.
In a remarkably interdependent manner, Metro and DLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Review rationale: Cell-junction localization is biologically supported by direct identification of Metro at larval neuromuscular junctions and its junctional scaffold complex. It is broader than the existing cell-cell-junction annotation, so the prediction is less precise. The source ARBA cell-junction row is annotation overlap only; the primary experiment provides independent support.
Supporting Evidence:
PMID:20427642: "In this study we have identified Metro, a novel p55/MPP-like Drosophila MAGUK as a major binding partner of perisynaptic DlgS97 at larval NMJs."
PMID:20427642: "Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7."