Motor Protein Receptors Moonlighting on Other Jobs

Transport of cargo proteins between membrane-bound San Francisco, California 94143 organelles is generally thought to occur via carrier vesi-cles. The first step in this process is the self-assembly of coat proteins on the cytoplasmic side of the membrane, which acts to recruit cargo proteins and catalyze the The eukaryotic cytoplasm is a highly ordered, yet dy-formation of a budding vesicle. Clathrin and coatomer namic environment. Within the cell, large membrane-proteins (COPs) are the principal coat proteins that func-bound organelles create compartments that carry out tion in this capacity, and they are used to shuttle cargo distinct biochemical processes, while smaller vesicles between membranes in distinct steps of the secretory act as carriers that deliver proteins and lipids between pathway. Coat subunits interact with the surface of an these compartments. As examples, proteins destined organelle through " adaptor " proteins that provide addi-for secretion are inserted into the endoplasmic reticulum tional specificity and are needed for the coating and (ER), processed in the Golgi, and then delivered to the budding processes. cell surface; endocytosed vesicles, on the other hand, In this issue of Cell, the AP-1 clathrin-associated are transported centripetally from the plasma membrane adaptor complex, which helps to mediate the transport to the cell interior for fusion with lysosomes. Mitochon-of clathrin-coated vesicles from the trans-Golgi network dria are also very dynamic organelles and are trans-(TGN) to plasma membrane, was found to bind to the ported to sites of high ATP consumption in the cyto-Kinesin-superfamily motor KIF13A (Nakagawa et al., plasm. 2000). This finding emerged from affinity purifications Over the past decade, it has become apparent that of AP1-␤1-adaptin with recombinant KIF13A-GST fusion overall membrane organization and the shuttling of vesi-proteins, and coimmunprecipitations from extracts. This cles both require cytoskeletal filaments and molecular interaction was further confirmed by two-hybrid interac-motor proteins (Allan and Schroer, 1999). All three motor tions that showed that the carboxy-terminal tail domain protein superfamilies are involved in membrane trans-of KIF13A bound to the " ear " domain of AP1-␤1-adaptin. port: several types of kinesin motors transport vesicular KIF13A also partially colocalizes with AP-1, as both cargo toward the microtubule plus-end, cytoplasmic show prominent immunofluorescence staining on the dynein transports membranes toward the microtubule Golgi apparatus. Overexpression of KIF13A causes mis-minus-end, and certain classes of unconventional myo-localization of AP-1 as well as a reduction in the plasma sins convey cargo along actin filaments. Many of these membrane appearance …