The kinesin KIF1C and microtubule plus ends regulate podosome dynamics in macrophages
Open accessAbstract
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.
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Additional Rab6A effectors BICDR-1 and myosin IIA interact at least indirectly with KIF1C.
“In addition to the direct interaction between Rab6A and KIF1C described here, additional Rab6A effectors have been reported to interact at least indirectly with KIF1C. These include BICDR-1, which interacts in lysates and by yeast two-hybrid at the C-terminus of KIF1C (Schlager et al., 2010), and myosin IIA, which in lysates, interacts in the region before the C-terminus (residues 713–811; Kopp et”
From The Rab6-regulated KIF1C kinesin motor domain contributes to Golgi organization (2015) · cites this paper as Kopp et al., 2006
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The Rab6-regulated KIF1C kinesin motor domain contributes to Golgi organization
Lee, P. L., Ohlson, M. B., & Pfeffer, S. R. (2015) · eLife · doi:10.7554/elife.06029 · Cited by 65 · see citing works
- Authors
- Kopp, P., Lammers, R., Aepfelbacher, M., Woehlke, G., Rudel, T., Machuy, N., Steffen, W., & Linder, S.
- Affiliations
- Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten (DE)
- University of Tübingen (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Ludwig-Maximilians-Universität München (DE)
- Max Planck Society (DE)
- Medizinische Hochschule Hannover (DE)
- Venue
- Molecular Biology of the Cell
- Published
- 2006-06
- Volume
- 17
- Issue
- 6
- Pages
- 2811-2823
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W2111139783
- Cited by
- 131
- References
- 44
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 8 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 10 · 2012: 11
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- KIF1C, kinesin-3, podosomes, microtubule plus ends, macrophages, non-muscle myosin IIA, cell migration, cell invasion
- MeSH terms
- Cell Differentiation, Cells, Cultured, Cloning, Molecular, Escherichia coli, Humans, Macrophages, Microinjections, Microtubules, Plasmids, Transfection, Mutagenesis, Kinesins, Reverse Transcriptase Polymerase Chain Reaction, Cell Membrane Structures, RNA, Small Interfering
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