MOCA induces membrane spreading by activating Rac1.
The modifier of cell adhesion protein (MOCA), or Dock3, initially identified as presenilin-binding protein (PBP), belongs to the Dock180 family of proteins and is localized specifically in neurons. Here we demonstrate that MOCA binds to Rac1 and enhances its activity, which leads to the activation of c-Jun NH(2)-terminal kinase (JNK) and causes changes in cell morphology. Farnesylated MOCA, which is localized in the plasma membrane, enhances the activation of Rac1 and JNK more markedly than wild-type MOCA, and cells expressing farnesylated MOCA show flattened morphology similar to those expressing a constitutive active mutant of Rac1, Rac1Q61L. On poly-d-lysine-coated dishes, endogenous MOCA is concentrated on the leading edge of broad membrane protrusions (lamellipodia) where actin filaments are co-localized. MOCA is also concentrated with actin on the growth cone in primary cultures of cortical neurons. These observations suggest that MOCA may induce cytoskeletal reorganization and changes in cell adhesion by regulating the activity of Rac1.
Namekata
Kazuhiko
K
National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan.
Enokido
Yasushi
Y
Iwasawa
Kazu
K
Kimura
Hideo
H
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D019922:GAP-43 Protein / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D017368:Protein Prenylation; D017434:Protein Structure, Tertiary; D011817:Rabbits; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D000906:Antibodies; D002352:Carrier Proteins; C485840:DOCK3 protein, human; C410623:Dock3 protein, mouse; D019922:GAP-43 Protein; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D006160:Guanosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein