Cofiline

Cofilin, often spelled cofiline in some sources, is an actin-binding protein that participates in the remodeling of the actin cytoskeleton in eukaryotic cells. It belongs to the ADF/cofilin family, which also includes actin-depolymerizing factor (ADF). In vertebrates, two major isoforms exist: cofilin-1 (CFL1), expressed broadly, and cofilin-2 (CFL2), more restricted to muscle tissue.

Function: Cofilin binds to ADP-actin subunits within F-actin and induces filament severing and accelerated depolymerization, increasing actin turnover and generating new filament ends for polymerization. This activity is modulated by cellular signaling pathways and by the nucleotide state of actin.

Regulation: The activity of cofilin is tightly controlled by phosphorylation at Ser3. Phosphorylation by LIM kinases (LIMK1 and LIMK2) inactivates cofilin. Dephosphorylation by phosphatases such as SSH1L reactivates it. Other regulators include p21-activated kinases, 14-3-3 proteins that sequester phosphorylated cofilin, and interactions with actin-binding partners like AIP1, coronin, and cortactin that can enhance severing.

Biological roles: Cofilin-mediated actin turnover is essential for cell motility, chemotaxis, endocytosis, cytokinesis, and morphological changes in developing neurons. In neurons, cofilin activity influences growth cone dynamics and synaptic plasticity.

Clinical relevance: Dysregulation of cofilin signaling has been linked to cancer cell invasion and metastasis, neuronal damage in neurodegenerative diseases, and aspects of synaptic dysfunction.

See also: ADF/cofilin family, actin cytoskeleton, LIMK, SSH phosphatases.