The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes

Susanne Cornfine, Mirko Himmel, Petra Kopp, Karim El Azzouzi, Christiane Wiesner, Marcus Krüger, Thomas Rudel, Stefan Linder

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Podosomes are actin-based matrix contacts in a variety of cell types, most notably monocytic cells, and are characterized by their ability to lyse extracellular matrix material. Besides their dependence on actin regulation, podosomes are also influenced by microtubules and microtubule-dependent transport processes. Here we describe a novel role for KIF9, a previously little-characterized member of the kinesin motor family, in the regulation of podosomes in primary human macrophages. We find that small interfering RNA (siRNA)/short-hairpin RNA-induced knockdown of KIF9 significantly affects both numbers and matrix degradation of podosomes. Overexpression and microinjection experiments reveal that the unique C-terminal region of KIF9 is crucial for these effects, presumably through binding of specific interactors. Indeed, we further identify reggie-1/flotillin-2, a signaling mediator between intracellular vesicles and the cell periphery, as an interactor of the KIF9 C-terminus. Reggie-1 dynamically colocalizes with KIF9 in living cells, and, consistent with KIF9-mediated effects, siRNA-induced knockdown of reggies/flotillins significantly impairs matrix degradation by podosomes. In sum, we identify the kinesin KIF9 and reggie/flotillin proteins as novel regulators of macrophage podosomes and show that their interaction is critical for the matrix-degrading ability of these structures.

Original languageEnglish
Pages (from-to)202-215
Number of pages14
JournalMolecular Biology of the Cell
Volume22
Issue number2
DOIs
StatePublished - 15 Jan 2011
Externally publishedYes

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