Podosomes are dynamic, actin-rich structures that facilitate remodelling of the extracellular matrix (ECM); they are found in cells that rely on ECM remodelling for their physiological function (e.g. in angiogenesis and vascular repair). Microtubules (MTs) have been shown to regulate podosomes and several MT-dependent motors are involved in podosome formation. Among these is the kinesin KIF1C, which has been proposed to affect podosome dynamics by transporting essential components, such as integrins. In their study on page (5179), Irina Kaverina and co-workers now investigate how KIF1C is activated upon podosome induction by protein kinase C (PKC) in rat aortic vascular smooth muscle cells (VSMCs). They show that PKC activation results in an MT-dependent delivery of KIF1C to the cell periphery where podosomes eventually form. Owing to the observed dynamics of the KIF1C puncta, the authors reason that MT-plus-end binding proteins (+TIPs) might be involved in KIF1C translocation and, indeed, show that CLIP-associated proteins (CLASPs) are required, as CLASP depletion abolishes the accumulation of KIF1C at the cell periphery without affecting overall KIF1C levels. Furthermore, depletion of either KIF1C or of CLASPs inhibits podosome formation, strongly indicating that CLASP-mediated transport of KIF1C along MTs is part of the signalling cascade downstream of PKC that is required to induce podosome formation. Moreover, this work also provides the first direct evidence that CLASPs regulate molecular motor function.

© 2014. Published by The Company of Biologists Ltd
2014