Kinesins mediate trafficking of membrane-bounded organelles towards microtubule plus-ends. Different proteins and cargos are targeted for different locations, but, until recently, little was known about regulation of kinesin-based motility. Phosphorylation of kinesin light chains by glycogen synthase kinase 3 (GSK-3) [1xGlycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. Morfini, G et al. EMBO J. 2002; 23: 281–293Crossref | Scopus (261)See all References[1] has now been shown to provide one such regulatory mechanism. GSK-3 inhibits anterograde, but not retrograde, transport in squid axoplasm and reduces amounts of kinesin bound to membranes. Kinesin activities other than cargo binding are unaffected by GSK-3 phosphorylation. As predicted, active GSK-3 is localized preferentially in regions known to be sites of membrane delivery.In this set of images (Fig. 1Fig. 1), distributions for tubulin [green; (c)] and total GSK-3 [red; (a)] are compared in a rat hippocampal neuron and oligodendrocyte. Microtubule-containing regions in both neurons and glia co-label for GSK-3 [yellow (b)]. This distribution is similar to that seen for kinesin [1.xGlycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. Morfini, G et al. EMBO J. 2002; 23: 281–293Crossref | Scopus (261)See all References, 2.xMonoclonal antibodies to kinesin heavy and light chains stain vesicle-like structures, but not microtubules, in cultured cells. Pfister, K.K et al. J. Cell Biol. 1989; 108: 1453–1463Crossref | PubMedSee all References]. However, in locations where membrane proteins are delivered, such as tips of elongating processes (i.e. growth cones) or membrane sheets of oligodendrocytes, GSK-3 immunoreactivity is distinct from that of microtubules. Moreover, the GSK-3 in growth cones and similar regions is preferentially activated, consistent with a role for GSK-3 phosphorylation of kinesin in regulating delivery of some membrane proteins to specific subcellular domains.Fig. 1Localization of glycogen synthase kinase 3 [GSK-3; (a)] and tubulin (c) in a rat hippocampal neuron and oligodendrocyte. In the merged image (b), GSK-3 is shown in red and tubulin in green; colocalization is shown in yellow. Rat hippocampal cultures were a generous gift of Ann Marie Craig, Washington University, St Louis, MO, USA.View Large Image | Download PowerPoint Slide