RRC ID 45659
著者 Xu Y, Taru H, Jin Y, Quinn CC.
タイトル SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) function interdependently to promote axon guidance by regulating the MIG-2 GTPase.
ジャーナル PLoS Genet
Abstract During development, axons must integrate directional information encoded by multiple guidance cues and their receptors. Axon guidance receptors, such as UNC-40 (DCC) and SAX-3 (Robo), can function individually or combinatorially with other guidance receptors to regulate downstream effectors. However, little is known about the molecular mechanisms that mediate combinatorial guidance receptor signaling. Here, we show that UNC-40, SAX-3 and the SYD-1 RhoGAP-like protein function interdependently to regulate the MIG-2 (Rac) GTPase in the HSN axon of C. elegans. We find that SYD-1 mediates an UNC-6 (netrin) independent UNC-40 activity to promote ventral axon guidance. Genetic analysis suggests that SYD-1 function in axon guidance requires both UNC-40 and SAX-3 activity. Moreover, the cytoplasmic domains of UNC-40 and SAX-3 bind to SYD-1 and SYD-1 binds to and negatively regulates the MIG-2 (Rac) GTPase. We also find that the function of SYD-1 in axon guidance is mediated by its phylogenetically conserved C isoform, indicating that the role of SYD-1 in guidance is distinct from its previously described roles in synaptogenesis and axonal specification. Our observations reveal a molecular mechanism that can allow two guidance receptors to function interdependently to regulate a common downstream effector, providing a potential means for the integration of guidance signals.
巻・号 11(4)
ページ e1005185
公開日 2015-4-1
DOI 10.1371/journal.pgen.1005185
PII PGENETICS-D-14-02315
PMID 25876065
PMC PMC4398414
MeSH Animals Axons / metabolism* Axons / physiology Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Neurogenesis* Protein Binding Receptors, Immunologic / genetics Receptors, Immunologic / metabolism* Signal Transduction rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism*
IF 5.175
引用数 8
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm6234 tm5504