Regulation of SNARE assembly by protein phosphorylation

Protein phosphorylation is emerging as an important regulatory mechanism that controls the secretory pathway. It enables coupling between the vesicular transport machinery and signaling cascades that are activated by both internal and external stimuli. Proteins that mediate the last steps of membrane fusion such as SNAREs, Sec1/Munc18, Rab proteins, and others undergo post-translational modification by phosphorylation to control membrane fusion. Control of fusion by protein phosphorylation is operant in both constitutive and regulated exocytic processes, and appears to regulate transport throughout the secretory pathway. The kinases involved are diverse and represent various signaling paths, including those of protein kinase A (PKA), PKC, casein kinase, death-associated protein kinase (DAPK), calcium/calmodulin-dependent protein kinase II (CaMKII), and cyclindependent kinase (Cdk). The phosphatases include protein phosphatase 1 (PP1) and ceramide-activated protein phosphatase (CAPP). Here, we present an overview on most recent information available concerning phosphorylative control of SNARE assembly leading to membrane fusion.