prom1b

UniProt ID: A0A8M2BI60
Organism: Danio rerio
Review Status: COMPLETE
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Gene Description

prom1b (prominin 1 b) is one of two zebrafish co-orthologs of vertebrate PROM1 (prominin-1, CD133), retained from the teleost-specific genome duplication; its paralog is prom1a. It encodes a pentaspan membrane glycoprotein of the prominin family, which sits in cholesterol-rich protrusions of the apical plasma membrane; a GFP fusion of Prom1b is enriched at the apical surface of retinal neuroepithelial cells. prom1b is zygotic only, rises strongly at 3-5 dpf, and is the more abundant prominin transcript in rod and cone photoreceptors; it is also expressed on the scleral side of the retinal inner nuclear layer, in the pineal organ, and in adult brain germinative zones of the hindbrain. Loss of prom1b disrupts photoreceptor outer-segment morphogenesis and causes early cone degeneration, while rods survive with abnormal outer segments; the outer-segment protein Prph2 is mislocalized and its oligomerization disrupted. This matches the role of mammalian PROM1 in outer-segment disc formation and retinal degeneration.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0016020 membrane
IEA
GO_REF:0000002
ACCEPT
Summary: Membrane, from the prominin InterPro signature.
Reason: Correct; Prom1b is a multi-pass membrane protein with the five transmembrane segments of the family.
Supporting Evidence:
file:DANRE/prom1a/prom1a-bioinformatics/RESULTS.md
All five transmembrane segments of human PROM1 align without gaps in both copies
GO:0016324 apical plasma membrane
IDA
PMID:22492354
Loss of Llgl1 in retinal neuroepithelia reveals links betwee...
ACCEPT
Summary: Apical plasma membrane, from a Prom1b-GFP transgene used as an apical marker in retinal neuroepithelia.
Reason: Direct localization of the tagged zebrafish protein, consistent with the conserved apical location of prominins.
Supporting Evidence:
PMID:22492354
We also generated a transgenic line in which GFP is fused with Prominin1b (Prom1b-GFP), a cholesterol-interacting pentaspan membrane protein that is enriched at the apical region of polarized cells, including retinal neuroepithelia
GO:0031528 microvillus membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Microvillus membrane, from an ARBA-derived UniProt subcellular location.
Reason: Family-level location of prominins; no zebrafish data, but nothing argues against it.
Supporting Evidence:
PMID:32201384
They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof.
GO:0035845 photoreceptor cell outer segment organization
IMP
PMID:31362982
Deletion of the transmembrane protein Prom1b in zebrafish di...
ACCEPT
Summary: Photoreceptor outer segment organization, from prom1b knockout zebrafish with disrupted outer-segment morphogenesis.
Reason: Core process. The prom1b mutant phenotype (malformed outer segments in rods and cones, cone degeneration, mislocalized Prph2) reproduces the structural role of mammalian PROM1 in disc morphogenesis, and the protein is expressed in photoreceptors. Only the abstract is cached; the full text on PMC describes a frameshift allele.
Supporting Evidence:
PMID:31362982
Loss of prom1b disrupted OS morphogenesis, with rods and cones exhibiting differences in impairment: cones degenerated at an early age, whereas rods remained viable but with an abnormal OS, even at 9 months postfertilization.
PMID:31362982
Moreover, we found that Prom1b deletion causes mislocalization of Prph2 and disrupts its oligomerization.

Core Functions

Pentaspan prominin glycoprotein of photoreceptors and apical membranes, required for outer-segment morphogenesis and for proper localization and oligomerization of Prph2; the photoreceptor-dominant zebrafish PROM1 co-ortholog.

Supporting Evidence:
  • PMID:31362982
    The Prom1 orthologs in zebrafish include prom1a and prom1b, and our results showed that prom1b, rather than prom1a, plays an important role in zebrafish photoreceptors.
  • PMID:21407811
    Of the two prominin-1 paralogues, expression of prominin-1b appeared to be more robust in line with gene expression profiling reported earlier on embryonic retina [33].

References

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Suggested Questions for Experts

Q: Where is Prom1b in the zebrafish photoreceptor (outer-segment base, rim, calyceal processes)? The published antibody did not work for immunofluorescence.

Q: Is prom1a upregulated in prom1b mutants, and would a prom1a; prom1b double mutant worsen the rod phenotype?

Suggested Experiments

Experiment: Knock in an epitope tag at prom1b and image it by expansion or immuno-electron microscopy in rods and cones, together with Prph2 and Cdhr1a.

Hypothesis: Prom1b acts at the base of nascent discs with Cdhr1a and Prph2, as mammalian PROM1 does.

Type: localization

πŸ“š Additional Documentation

Notes

(prom1b-notes.md)

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