title: Myosin-Va-interacting protein, RILPL2, controls cell shape and neuronal morphogenesis via Rac signaling.
abstract: Neuronal morphology plays an essential role in neuronal function. The establishment and maintenance of neuronal morphology is intimately linked to the actin cytoskeleton; however, the molecular mechanisms that regulate changes in neuronal morphology are poorly understood. Here we identify a novel myosin-Va (MyoVa)-interacting protein, RILPL2, which regulates cellular morphology. Overexpression of this protein in young or mature hippocampal neurons results in an increase in the number of spine-like protrusions. By contrast, knockdown of endogenous RILPL2 in neurons by short hairpin RNA (shRNA) interference results in reduced spine-like protrusions, a phenotype rescued by overexpression of an shRNA-insensitive RILPL2 mutant, suggesting a role for RILPL2 in both the establishment and maintenance of dendritic spines. Interestingly, we demonstrate that RILPL2 and the Rho GTPase Rac1 form a complex, and that RILPL2 is able to induce activation of Rac1 and its target, p21-activated kinase (Pak). Notably, both RILPL2-mediated morphological changes and activation of Rac1-Pak signaling were blocked by expression of a truncated tail form of MyoVa or MyoVa shRNA, demonstrating that MyoVa is crucial for proper RILPL2 function. This might represent a novel mechanism linking RILPL2, the motor protein MyoVa and Rac1 with neuronal structure and function.
authors.affiliation: Department of Psychiatry and Brain Research Center, University of British Columbia, Vancouver, BC, Canada. marief.lise@gmail.com
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Lisé
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Srivastava
authors.forename: Pamela
authors.initials: P
authors.lastname: Arstikaitis
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Lett
authors.forename: Razan
authors.initials: R
authors.lastname: Sheta
authors.forename: Vijay
authors.initials: V
authors.lastname: Viswanathan
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
authors.forename: Timothy P
authors.initials: TP
authors.lastname: O'Connor
authors.forename: Alaa
authors.initials: A
authors.lastname: El-Husseini
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D048430:Cell Shape; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005799:Genes, Dominant; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024701:Myosin Type V / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D009928:Organ Specificity; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C513081:Myo5a protein, rat; D012333:RNA, Messenger; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D020744:rac GTP-Binding Proteins