Myosin-Va-interacting protein, RILPL2, controls cell shape and neuronal morphogenesis via Rac signaling.
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.
Lisé
Marie-France
MF
Department of Psychiatry and Brain Research Center, University of British Columbia, Vancouver, BC, Canada. marief.lise@gmail.com
Srivastava
Deepak P
DP
Arstikaitis
Pamela
P
Lett
Robyn L
RL
Sheta
Razan
R
Viswanathan
Vijay
V
Penzes
Peter
P
O'Connor
Timothy P
TP
El-Husseini
Alaa
A
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*
D002352:Carrier Proteins; C513081:Myo5a protein, rat; D012333:RNA, Messenger; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D020744:rac GTP-Binding Proteins