Cited by 113Axon Guidance and Neuronal SignalingNeuroscience and Neuropharmacology ResearchDevelopmental Biology and Gene Regulation

The Two Isoforms of the Caenorhabditis elegans Leukocyte-Common Antigen Related Receptor Tyrosine Phosphatase PTP-3 Function Independently in Axon Guidance and Synapse Formation

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Ackley, Brian D., Harrington, Robert J., Hudson, Martin L., Williams, Lisa, Kenyon, Cynthia J., Chisholm, Andrew D., Jin, Yishi·2005·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.2010-05.2005

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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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Research works printed but not linked: 1

  1. Williams L (2002) A genetic analysis of the left-right asymmetric polariza- tions and migrations of the Q neuroblasts in Caenorhabditis elegans. PhD thesis, University of California, San Francisco.

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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
Published
2005-08-17
Volume
25
Issue
33
Pages
7517-7528
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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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