MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF CHROMAFFIN CELL SCINDERIN INDICATES THAT IT BELONGS TO THE FAMILY OF CA2-DEPENDENT F-ACTIN SEVERING PROTEINS()

Scinderin is a Ca+-dependent actin filament severing protein present i n chromaffin cells, platelets and a variety of secretory cells. It has been suggested that scinderin is involved in chromaffin cell F-actin dynamics and that this actin network controls the delivery of secretor y vesicles to plasma membrane exocytotic sites. Moreover, scinderin re distribution and activity may be regulated by pH and Ca2+ in resting a nd stimulated cells. Here we describe the molecular cloning, the nucle otide sequence and the expression of bovine chromaffin cell scinderin cDNA. The fusion protein obtained cross-reacts with native scinderin a ntibodies and binds phosphatidylserine (PS), phosphatidylinositol 4,5- bisphosphate (PIP2) and actin in a Ca+-dependent manner. Antibodies ra ised against the fusion protein produced the same cellular staining pa tterns for scinderin as anti-native scinderin. Nucleotide and amino ac id sequence analysis indicate that scinderin has six domains each cont aining three internal sequence motifs, two actin and two PIP2 binding sites and has 63 and 53% homology with gelsolin and villin. These data indicate that scinderin is a novel member of the family of Ca2+-depen dent F-actin severing proteins which includes gelsolin and villin.