The Actin Nucleator Cobl Is Controlled by Calcium and Calmodulin

Area of Science:

• Cell Biology
• Neuroscience
• Biochemistry

Background:

• Actin nucleation is crucial for cell shape and requires strict regulation.
• WASP Homology 2 (WH2) domain-based actin nucleators, like Cordon-Bleu (Cobl), are novel but poorly understood.
• Cobl plays a role in neuronal arborization, but its regulatory mechanisms are largely elusive.

Purpose of the Study:

• To elucidate the signal cascades and mechanisms regulating the actin nucleator Cordon-Bleu (Cobl).
• To investigate the role of calcium (Ca2+) and Calmodulin (CaM) in Cobl-mediated actin nucleation and neuronal branching.

Main Methods:

• Overexpression analyses and rescue experiments in primary neurons and tissue slices.
• Ca2+ imaging and F-actin/CaM accumulation studies at dendritic protrusion sites.
• CaM inhibitor studies and mechanistic investigations of Cobl-Ca2+/CaM interactions.

Main Results:

• Cobl actin nucleation is directly regulated by Ca2+ and Calmodulin (CaM) through multiple binding associations.
• CaM binding is critical for Cobl's function in dendritic branch initiation, which is preceded by Ca2+ signals.
• Ca2+/CaM modulates Cobl's actin binding and enhances its interaction with syndapin I at nascent protrusions.

Conclusions:

• Ca2+/CaM directly regulates the WH2 domain-based actin nucleator Cobl.
• Ca2+/CaM-controlled mechanisms are essential for Cobl's cellular functions in actin formation.
• Local Ca2+ signals, via CaM-mediated Cobl regulation, drive branch initiation in neuronal arborization.