Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells

Adenomatous polyposis coli (APC) tumor suppressor protein has been shown to be localized near the distal ends of microtubules (MTs) at the edges of mi grating cells. We expressed green fluorescent protein (GFP)-fusion proteins with full-length and deletion mutants of Xenopus APC in Xenopus epithelial cells, and observed their dynamic behavior in live cells. During cell spre ading and wound healing, GFP-tagged full-length APC was concentrated as gra nules at the tip regions of cellular extensions. At higher magnification, A PC appeared to move along MTs and concentrate as granules at the growing pl us ends. When MTs began to shorten, the APC granules dropped off from the M T ends. Immunoelectron microscopy revealed that fuzzy structures surroundin g MTs were the ultrastructural counterparts for these GFP signals. The COOH -terminal region of APC was targeted to the growing MT ends without forming granular aggregates, and abruptly disappeared when MTs began to shorten. T he APC lacking the COOH-terminal region formed granular aggregates that mov ed along MTs toward their plus ends in an ATP-dependent manner. These findi ngs indicated that APC is a unique MT-associated protein that moves along s elected MTs and concentrates at their growing plus ends through their multi ple functional domains.