The Kinesin KIF1C and Microtubule Plus Ends Regulate Podosome Dynamics in Macrophages

Kopp P, Lammers R, Aepfelbacher M, Woehlke G, Rudel T, Machuy N, Steffen W, Linder S
Source: Mol Biol Cell
Publication Date: (2006)
Issue: 17(6): 2811-2823
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
Macrophage, human
Species: human
Tissue Origin: blood
Nucleofector® I/II/2b
Microtubules are important for the turnover of podosomes, dynamic, actin-rich adhesions implicated in migration and invasion of monocytic cells. The molecular basis for this functional dependency, however, remained unclear. Here, we show that contact by microtubule plus-ends critically influences the cellular fate of podosomes in primary human macrophages. In particular, we identify the kinesin KIF1C, a member of the Kinesin-3 family, as a plus-end-enriched motor which targets regions of podosome turnover. Expression of mutation constructs or siRNA-/shRNA-based depletion of KIF1C resulted in decreased podosome dynamics and ultimately in podosome deficiency. Importantly, protein interaction studies showed that KIF1C binds to nonmuscle myosin IIA via its PTPD-binding domain, thus providing an interface between the actin and tubulin cytoskeletons, which may facilitate the subcellular targeting of podosomes by microtubules. This is the first report to implicate a kinesin in podosome regulation and also the first to describe a function for KIF1C in human cells.