Box 2 | Modes of motor–cargo association

From the following article:

Powering membrane traffic in endocytosis and recycling

Thierry Soldati and Manfred Schliwa

Nature Reviews Molecular Cell Biology 7, 897-908 (December 2006)

doi:10.1038/nrm2060

Only a subset of myosin, kinesin and dynein motors have so far been shown to power vesicular trafficking (Fig. 1). Cargo association involves non-motor domains and, in many cases, accessory proteins. Three types of cargo-association mechanism can be distinguished.

Association with membrane lipids. Essentially all of the class-I myosins have a polybasic domain that has an affinity for membranes23 (panel a). Some members of the kinesin-3 family, such as UNC104, bind to phospholipids directly through their pleckstrin-homology (PH) domain and can cluster in lipid rafts, facilitating dimerization35. PH domains are also present in myosin X, but it is not known whether this motor is involved in vesicle movement. Dictyostelium discoideum MyoM contains a Rac guanine-nucleotide exchange factor domain that has a PH subdomain134 and associates with macropinocytic structures135. Last, genome mining revealed a human myosin that contains a FYVE domain that is thought to interact with endosomal phosphatidylinositol-3-phosphate136.

Powering membrane traffic in endocytosis and recycling 

Binding to integral membrane proteins. Examples include kinesin-1, which has been proposed to interact directly with amyloid precursor protein137; however, data remain controversial138. Myosin Va interacts with syntaxin-1A in a Ca2+-dependent manner to regulate exocytosis106. In inner ear sensory cells, myosins Ia and VIIa interact with the integral membrane protein pleckstrin-homology domain retinal protein-1 (PHR1)19 (panel b).

Linkage through scaffolding complexes. This is thought to be the most widespread form of membrane–motor interaction. Kinesin-1, -2 and -3 (panel c) as well as myosin V and VI can bind to multisubunit adaptors that link them to membranes. A bulky activator complex, dynactin, is likely to be involved in regulating dynein targeting and recruitment to vesicular cargo, although the molecular details of its interactions have yet to be worked out66. Dynactin can bind to phospholipids and membrane-associated spectrin, providing a possible means for interaction with multiple membrane cargoes139. However, spectrin is not a crucial component of cargo binding in Caenorhabditis elegans neurons140. RAB proteins might be involved in cargo binding as well. For example, at the Golgi apparatus, RAB6, its interactor Bicaudal-D and Golgi-specific beta-III spectrin interact with distinct dynactin subunits and/or directly with dynein141, whereas at phagosomes, RAB7 and its interactor RAB7-interacting lysosomal protein (RILP) recruit the dynein–dynactin complex68.