Kinesin motors and primary cilia
Open accessAbstract
Cilia and flagella play important roles in human health by contributing to cellular motility as well as sensing and responding to environmental cues. Defects in ciliary assembly and/or function can lead to a range of human diseases, collectively known as the ciliopathies, including polycystic kidney, liver and pancreatic diseases, sterility, obesity, situs inversus, hydrocephalus and retinal degeneration. A basic understanding of how cilia form and function is essential for deciphering ciliopathies and generating therapeutic treatments. The cilium is a unique compartment that contains a distinct complement of protein and lipid. However, the molecular mechanisms by which soluble and membrane protein components are targeted to and trafficked into the cilium are not well understood. Cilia are generated and maintained by IFT (intraflagellar transport) in which IFT cargoes are transported along axonemal microtubules by kinesin and dynein motors. A variety of genetic, biochemical and cell biological approaches has established the heterotrimeric kinesin-2 motor as the ‘core’ IFT motor, whereas other members of the kinesin-2, kinesin-3 and kinesin-4 families function as ‘accessory’ motors for the transport of specific cargoes in diverse cell types. Motors of the kinesin-9 and kinesin-13 families play a non-IFT role in regulating ciliary beating or axonemal length, respectively. Entry of kinesin motors and their cargoes into the ciliary compartment requires components of the nuclear import machinery, specifically importin-β2 (transportin-1) and Ran-GTP (Ran bound to GTP), suggesting that similar mechanisms may regulate entry into the nuclear and ciliary compartments.
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Many studies in different organisms confirmed a universal requirement for heterotrimeric kinesin-2 and cytoplasmic dynein 2 in IFT, but some organisms also use accessory kinesins to regulate aspects of ciliary assembly or function.
“A large number of studies in different organisms subsequently confirmed a universal requirement for these motors in IFT, but also demonstrated that some organisms additionally use ‘accessory’ kinesins to regulate certain aspects of ciliary assembly or function 23, 39.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [39]
The Intraflagellar transport section (page unavailable) says heterotrimeric kinesin-2 is critical for anterograde IFT in every organism tested and identifies cytoplasmic dynein as the retrograde IFT motor. The IFT kinesins section (page unavailable) describes accessory kinesins with cell-specific roles in ciliary shape and function. The copy does not establish the claimed universal requirement for cytoplasmic dynein across organisms. (LLM, conf=0.84)
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- Authors
- Verhey, K. J., Dishinger, J., & Kee, H. L.
- Affiliations
- University of Michigan (US)
- ORCID
- Verhey, Kristen J.
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2011-09-21
- Volume
- 39
- Issue
- 5
- Pages
- 1120-1125
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- PMC
- PMC3538878
- OpenAlex
- W2062516545
- Cited by
- 79
- References
- 54
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 9 · 2017: 6 · 2016: 6 · 2015: 11 · 2014: 6 · 2013: 6 · 2012: 4
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM070862, R01GM070862)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- kinesin motors, primary cilia, ciliopathies, intraflagellar transport, kinesin-2, kinesin-3, kinesin-4, kinesin-13, axoneme, ciliary protein trafficking, RanGTP, nuclear import, ciliary beating
- MeSH terms
- Animals, Biological Transport, Cell Line, Cilia, Dyneins, Flagella, Humans, Microtubules, Kinesins, Molecular Motor Proteins, ran GTP-Binding Protein
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