Actin microfilaments et al.--the many components, effectors and regulators of epithelial cell endocytosis.
The aim of this review is to introduce the advances made over the past several years regarding the participation of actin and actin-associated proteins in clathrin-mediated endocytosis in simple cell models, and then to consider the evidence for the involvement of these effectors in apical clathrin-mediated endocytosis in epithelial cells. Basic mechanisms of clathrin-mediated endocytosis are initially addressed, followed by a detailed description of the actin cytoskeleton: its organization, function and, most importantly, the essential role played by proteins and signaling pathways responsible for the regulation of actin filament dynamics. Our focus then shifts to the GTPase, dynamin and its pivotal role as a bridge between various components of the clathrin endocytic machinery and the actin cytoskeleton. Mechanisms and effectors of dynamin-dependent endocytosis are then described, with a particular emphasis on novel proteins, which link dynamin to actin filaments. We consider additional effectors proposed to interact with actin to facilitate clathrin-mediated endocytosis in a dynamin-independent manner. The multiple roles which actin filaments are thought to play in endocytosis are addressed followed by a more detailed characterization of actin filament participation specifically in apical endocytosis. We conclude by discussing how these concepts may be integrated to improve drug internalization at the apical plasma membrane of epithelial cells.
Department of Pharmaceutical Sciences, USC School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Silvia R
SR
da Costa
Curtis T
CT
Okamoto
Sarah F
SF
Hamm-Alvarez
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000502:physiology*; D000818:Animals; D002966:Clathrin / Q000378:metabolism / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008954:Models, Biological
D000199:Actins; D002966:Clathrin; D003598:Cytoskeletal Proteins