The two isoforms of the Caenorhabditis elegans leukocyte-common antigen related receptor tyrosine phosphatase PTP-3 function independently in axon guidance and synapse formation

Brian D Ackley; Robert J Harrington; Martin L Hudson; Lisa Williams; Cynthia J Kenyon; Andrew D Chisholm; Yishi Jin

doi:10.1523/JNEUROSCI.2010-05.2005

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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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The two isoforms of the Caenorhabditis elegans leukocyte-common antigen related receptor tyrosine phosphatase PTP-3 function independently in axon guidance and synapse formation

Brian D Ackley, Robert J Harrington, Martin L Hudson, Lisa Williams, Cynthia J Kenyon, Andrew D Chisholm and Yishi Jin

The Journal of neuroscience, Vol.25(33), pp.7517-7528

08/17/2005

DOI: https://doi.org/10.1523/JNEUROSCI.2010-05.2005

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https://hdl.handle.net/2376/118019

PMCID: PMC6725402

PMID: 16107639

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https://doi.org/10.1523/JNEUROSCI.2010-05.2005View

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Abstract

Protein Tyrosine Phosphatase, Non-Receptor Type 11

Protein Tyrosine Phosphatases - biosynthesis

Animals, Genetically Modified

Axons - metabolism

Axons - physiology

Synapses - genetics

Receptor-Like Protein Tyrosine Phosphatases, Class 2

Nerve Tissue Proteins - genetics

Protein Isoforms - physiology

Protein Tyrosine Phosphatases - genetics

Animals

Synapses - metabolism

Protein Isoforms - biosynthesis

Nerve Tissue Proteins - biosynthesis

Caenorhabditis elegans Proteins - physiology

Receptors, Cell Surface - biosynthesis

Mutation

Caenorhabditis elegans Proteins - genetics

Intracellular Signaling Peptides and Proteins - genetics

Caenorhabditis elegans - enzymology

Caenorhabditis elegans Proteins - biosynthesis

Protein Isoforms - genetics

Receptors, Cell Surface - genetics

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 alpha-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 alpha-liprin during synaptogenesis.

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Title: The two isoforms of the Caenorhabditis elegans leukocyte-common antigen related receptor tyrosine phosphatase PTP-3 function independently in axon guidance and synapse formation
Creators: Brian D Ackley - Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Cruz, California 95064, USA
Robert J Harrington
Martin L Hudson
Lisa Williams
Cynthia J Kenyon
Andrew D Chisholm
Yishi Jin
Publication Details: The Journal of neuroscience, Vol.25(33), pp.7517-7528
Publisher: United States
Grant note: R01 GM054657 / NIGMS NIH HHS GM54657 / NIGMS NIH HHS NS35546 / NINDS NIH HHS
Identifiers: 99900547970101842
Language: English
Resource Type: Journal article