RalA and the exocyst complex influence neuronal polarity through PAR-3 and aPKC.
Neuronal polarization requires localized cytoskeletal changes and polarized membrane traffic. Here, I report that the small GTPase RalA, previously shown to control neurite branching, also regulates neuronal polarity. RalA depletion, or ectopic expression of constitutively active RalA in cultured neurons inhibit axon formation. However, expression of a constitutively active RalA mutant that is unable to interact with the exocyst complex has no effect on neuronal polarization. Furthermore, depletion of the Sec6, Sec8 or Exo84 subunits of the exocyst complex also leads to unpolarized neurons. Early stages of neuronal polarization are accompanied by increasing levels of interaction of the exocyst complex with PAR-3 and atypical protein kinase C (aPKC), and by the RalA-dependent association of the exocyst complex with PAR-3. Thus, neuronal polarization involves a RalA-regulated association between mediators of vesicle trafficking (exocyst complex) and cell polarity (PAR-3).
Lalli
Giovanna
G
The Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK. giovanna.lalli@kcl.ac.uk
D000818:Animals; D001369:Axons / Q000201:enzymology; D002352:Carrier Proteins / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology / Q000201:enzymology*; D008565:Membrane Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D022161:Transport Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C096102:Exoc3 protein, rat; C076326:Exoc4 protein, rat; C502593:Exoc8 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C; C492197:Rala protein, rat; D020725:ral GTP-Binding Proteins