The kinesin KIF1C and microtubule plus ends regulate podosome dynamics in macrophages.
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 that targets regions of podosome turnover. Expression of mutation constructs or small interfering RNA-/short hairpin RNA-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.
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
Petra
P
Kopp
Reiner
R
Lammers
Martin
M
Aepfelbacher
Günther
G
Woehlke
Thomas
T
Rudel
Nikolaus
N
Machuy
Walter
W
Steffen
Stefan
S
Linder
D002454:Cell Differentiation; D021961:Cell Membrane Structures / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004926:Escherichia coli; D006801:Humans; D016547:Kinesins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008845:Microinjections; D008870:Microtubules / Q000502:physiology*; D016296:Mutagenesis; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C114063:KIF1C protein, human; D034741:RNA, Small Interfering; D016547:Kinesins