The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration.
Mutations in the adenomatous polyposis coli (APC) gene are linked to polyp formation in familial and sporadic colon cancer, but the functions of the protein are not known. We show that APC protein localizes mainly to clusters of puncta near the ends of microtubules that extend into actively migrating regions of epithelial cell membranes. This subcellular distribution of APC protein requires microtubules, but not actin filaments. APC protein-containing membranes are actively involved in cell migration in response to wounding epithelial monolayers, addition of the motorgen hepatocyte growth factor, and during the formation of cell-cell contacts. In the intestine, APC protein levels increase at the crypt/villus boundary, where cell migration is crucial for enterocyte exit from the crypt and where cells accumulate during polyp formation that is linked to mutations in the microtubule-binding domain of APC protein. Together, these data indicate that APC protein has a role in directed cell migration.
Näthke
I S
IS
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305-5426, USA.
Adams
C L
CL
Polakis
P
P
Sellin
J H
JH
Nelson
W J
WJ
D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure*; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells; D004848:Epithelium / Q000648:ultrastructure*; D019084:Fluorescent Antibody Technique, Indirect; D016147:Genes, Tumor Suppressor; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000648:ultrastructure; D008870:Microtubules / Q000648:ultrastructure*; D015534:Trans-Activators; D014741:Video Recording; D014945:Wound Healing; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D017228:Hepatocyte Growth Factor