Calmodulin dissociation regulates Myo5 recruitment and function at endocytic sites.
Myosins-I are conserved proteins that bear an N-terminal motor head followed by a Tail Homology 1 (TH1) lipid-binding domain. Some myosins-I have an additional C-terminal extension (C(ext)) that promotes Arp2/3 complex-dependent actin polymerization. The head and the tail are separated by a neck that binds calmodulin or calmodulin-related light chains. Myosins-I are known to participate in actin-dependent membrane remodelling. However, the molecular mechanisms controlling their recruitment and their biochemical activities in vivo are far from being understood. In this study, we provided evidence suggesting the existence of an inhibitory interaction between the TH1 domain of the yeast myosin-I Myo5 and its C(ext). The TH1 domain prevented binding of the Myo5 C(ext) to the yeast WIP homologue Vrp1, Myo5 C(ext)-induced actin polymerization and recruitment of the Myo5 C(ext) to endocytic sites. Our data also indicated that calmodulin dissociation from Myo5 weakened the interaction between the neck and TH1 domains and the C(ext). Concomitantly, calmodulin dissociation triggered Myo5 binding to Vrp1, extended the myosin-I lifespan at endocytic sites and activated Myo5-induced actin polymerization.
Grötsch
Helga
H
Department of Cellular Biology, Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Barcelona, Spain.
Giblin
Jonathan P
JP
Idrissi
Fatima-Zahra
FZ
Fernández-Golbano
Isabel-María
IM
Collette
John R
JR
Newpher
Thomas M
TM
Robles
Virginia
V
Lemmon
Sandra K
SK
Geli
María-Isabel
MI
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D004705:Endocytosis; D008840:Microfilament Proteins / Q000378:metabolism; D024461:Myosin Type I / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D002147:Calmodulin; C100412:MYO5 protein, S cerevisiae; D008840:Microfilament Proteins; D029701:Saccharomyces cerevisiae Proteins; C090350:VRP1 protein, S cerevisiae; D024461:Myosin Type I