A tripartite complex containing MRCK modulates lamellar actomyosin retrograde flow.
Actomyosin retrograde flow underlies the contraction essential for cell motility. Retrograde flow in both lamellipodia and lamella is required for membrane protrusion and for force generation by coupling to cell adhesion. We report that the Rac/Cdc42-binding kinase MRCK and myosin II-related MYO18A linked by the adaptor protein LRAP35a form a functional tripartite complex, which is responsible for the assembly of lamellar actomyosin bundles and of a subnuclear actomyosin network. LRAP35a binds independently to MYO18A and MRCK. This binding leads to MRCK activation and its phosphorylation of MYO18A, independently of ROK and MLCK. The MRCK complex moves in concert with the retrograde flow of actomyosin bundles, with MRCK being able to influence other flow components such as MYO2A. The promotion of persistent protrusive activity and inhibition of cell motility by the respective expression of wild-type and dominant-negative mutant components of the MRCK complex show it to be crucial to cell protrusion and migration.
Tan
Ivan
I
GSK-IMCB Group, Institute of Molecular & Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Yong
Jeffery
J
Dong
Jing Ming
JM
Lim
Louis
L
Leung
Thomas
T
D000205:Actomyosin / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D024462:Myosin Type II / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats
D000205:Actomyosin; D015815:Cell Adhesion Molecules; D024462:Myosin Type II; D009218:Myosins; D017346:Protein Serine-Threonine Kinases; C110936:Havcr1 protein, rat; C532580:MYO18A protein, rat; C532581:Cdc42bpa protein, rat