The Two Isoforms of the Caenorhabditis elegans Leukocyte-Common Antigen Related Receptor Tyrosine Phosphatase PTP-3 Function Independently in Axon Guidance and Synapse Formation
Open accessAbstract
Leukocyte-common antigen related (LAR)-like phosphatase receptors are conserved cell adhesion molecules that function in multiple developmental processes. The Caenorhabditis elegans ptp-3 gene encodes two LAR family isoforms that differ in the extracellular domain. We show here that the long isoform, PTP-3A, localizes specifically at synapses and that the short isoform, PTP-3B, is extrasynaptic. Mutations in ptp-3 cause defects in axon guidance that can be rescued by PTP-3B but not by PTP-3A. Mutations that specifically affect ptp-3A do not affect axon guidance but instead cause alterations in synapse morphology. Genetic double-mutant analysis is consistent with ptp-3A acting with the extracellular matrix component nidogen,nid-1, and the intracellular adaptor α-liprin,syd-2.nid-1 and syd-2 are required for the recruitment and stability of PTP-3A at synapses, and mutations in ptp-3 or nid-1 result in aberrant localization of SYD-2. Overexpression of PTP-3A is able to bypass the requirement for nid-1 for the localization of SYD-2 and RIM. We propose that PTP-3A acts as a molecular link between the extracellular matrix and α-liprin during synaptogenesis.
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α-Liprin is required for active zone formation with recruitment of synaptic vesicles and of LAR-type receptor phosphotyrosine phosphatases.
“Together, these data established that active zone formation with recruitment of synaptic vesicles and of LAR-type receptor phosphotyrosine phosphatases requires α-liprin, possibly by simultaneous binding of α-liprin to the receptor phosphotyrosine phosphatase, RIM, ELKS, Syd-1, and itself.”
From The Presynaptic Active Zone (2012) · cites this paper as Ackley et al., 2005
The Results section, “PTP-3 localization is dependent on nid-1 and syd-2” (page unavailable), supports a role for α-liprin/SYD-2 in recruiting the LAR-type receptor PTP-3 to synapses. The paper also reports altered synaptic-vesicle-marker puncta in syd-2 mutants. But “PTP-3A functions as a molecular linker at synapses” (page unavailable) explicitly says these proteins are required for the size and spacing of synaptic proteins, rather than synapse formation per se; it does not establish that α-liprin is required for active-zone formation or the proposed simultaneous binding. (LLM, conf=0.88)
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- Authors
- Ackley, B. D., Harrington, R. J., Hudson, M. L., Williams, L., Kenyon, C. J., Chisholm, A. D., & Jin, Y.
- Affiliations
- University of California, Santa Cruz (US)
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Jin, Yishi
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-08-17
- Volume
- 25
- Issue
- 33
- Pages
- 7517-7528
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725402
- OpenAlex
- W1984882339
- Cited by
- 113
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 12 · 2019: 6 · 2018: 10 · 2017: 3 · 2015: 7 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (NS35546)
- Muscular Dystrophy Association
- National Institutes of Health (GM54657)
- National Institute of General Medical Sciences (GM54657, R01GM054657)
- National Institute of Neurological Disorders and Stroke (R37NS035546, R01NS035546, NS35546)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Caenorhabditis elegans, isoform-specific function, axon guidance, synaptogenesis, synaptic morphology, nidogen, RIM, extracellular matrix, synaptic localization, adhesion molecules
- MeSH terms
- Animals, Axons, Mutation, Nerve Tissue Proteins, Receptors, Cell Surface, Synapses, Protein Tyrosine Phosphatases, Caenorhabditis elegans, Protein Isoforms, Caenorhabditis elegans Proteins, Animals, Genetically Modified, Intracellular Signaling Peptides and Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Receptor-Like Protein Tyrosine Phosphatases, Class 2
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