Calmodulin dissociation regulates Myo5 recruitment and function at endocytic sites

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Myosins-I are crucial for actin-dependent membrane remodeling.
• Their recruitment and in vivo biochemical activities remain poorly understood.
• Some myosins-I possess a C-terminal extension (C(ext)) that drives actin polymerization.

Purpose of the Study:

• To investigate the regulatory mechanisms of yeast myosin-I (Myo5) activity.
• To elucidate the role of the Tail Homology 1 (TH1) domain and C(ext) in Myo5 function.
• To understand how calmodulin binding affects Myo5 recruitment and actin polymerization.

Main Methods:

• Investigated protein-protein interactions using yeast models.
• Assessed the impact of domain interactions on actin polymerization.
• Analyzed protein localization and lifespan at endocytic sites in vivo.

Main Results:

• The TH1 domain of Myo5 inhibits its C(ext) from binding Vrp1 and inducing actin polymerization.
• Calmodulin dissociation weakens the interaction between the neck, TH1, and C(ext) domains.
• Calmodulin dissociation triggers Myo5 binding to Vrp1, prolongs Myo5 presence at endocytic sites, and activates actin polymerization.

Conclusions:

• An inhibitory interaction exists between the TH1 domain and C(ext) in yeast Myo5.
• Calmodulin acts as a negative regulator, dissociating to release this inhibition.
• This mechanism controls Myo5 recruitment and actin polymerization activity at endocytic sites.