Interaction of Doc2 with tctex-1, a Light Chain of Cytoplasmic Dynein

Abstract

Doc2 has one Munc13-interacting domain at the N- terminal region and two C2-like domains interacting with Ca2 and phospholipid at the C-terminal region. Doc2 consists of two isoforms, Doc2 and - known. We show here that both Doc2 . Doc2 is specifically expressed in neuronal cells and implicated in Ca2-dependent neurotransmitter release, whereas Doc2 is ubiquitously expressed and its function is un- and - interact with rat tctex-1, a light chain of cytoplasmic dynein, in both cell-free and intact cell systems. Overexpression of the N-terminal fragment of Doc2 containing the tctex-1- interacting domain induces changes in the intracellular localization of cation-independent mannose 6-phos- phate receptor and its ligand, cathepsin D, which are transported from trans-Golgi network to late endo- somes. Overexpression of the C-terminal fragment con- taining two C2-like domains shows the similar effect, but to a lesser extent, whereas overexpression of full- length Doc2 or the C-terminal fragment of rabphilin3 containing two C2-like domains does not show this ef- fect. Because dynein is a minus-end-directed microtu- bule-based motor protein, these results suggest that Doc2, especially Doc2 , plays a role in dynein-depend- ent intracellular vesicle transport.