The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Identification of Signaling Pathways Regulating Primary Cilium Length and Flow-Mediated Adaptation
Open accessAbstract
Summary The primary cilium acts as a transducer of extracellular stimuli into intracellular signaling [1, 2]. Its regulation, particularly with respect to length, has been defined primarily by genetic experiments and human disease states in which molecular components that are necessary for its proper construction have been mutated or deleted [1]. However, dynamic modulation of cilium length, a phenomenon observed in ciliated protists [3, 4], has not been well-characterized in vertebrates. Here we demonstrate that decreased intracellular calcium (Ca2+) or increased cyclic AMP (cAMP), and subsequent PKA activation, increases primary cilium length in mammalian epithelial and mesenchymal cells. Anterograde intraflagellar transport is sped up in lengthened cilia, potentially increasing delivery flux of cilium components. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases mechanotransductive signaling. This adaptive response is blocked when the autosomal dominant polycystic kidney disease (ADPKD) gene products, polycystin-1 or -2, are reduced. Dynamic regulation of cilium length is thus intertwined with cilium-mediated signaling and provides a natural braking mechanism in response to external stimuli that may be compromised in PKD.
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Cites
Calcium's Role in Mechanotransduction during Muscle Development
Benavides Damm, T., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,502
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells
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Self-citationOverview of Structure and Function of Mammalian Cilia
Satir, P., & Christensen, S. T. (2007) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.040705.141236 · Cited by 1,142 · cited 1×
“The primary cilium acts as a transducer of extracellular stimuli into intracellular signaling [1,2].”
A motility in the eukaryotic flagellum unrelated to flagellar beating.
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Microtubule Acetylation Promotes Kinesin-1 Binding and Transport
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Bending the MDCK Cell Primary Cilium Increases Intracellular Calcium
Praetorius, H. A., & Spring, K. R. (2001) · Journal of Membrane Biology · doi:10.1007/s00232-001-0075-4 · Cited by 828
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FLAGELLAR ELONGATION AND SHORTENING IN CHLAMYDOMONAS
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Cited by
Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity
Hopp, K., Ward, C. J., Hommerding, C. J., Nasr, S. H., Tuan, H.-F., Gainullin, V. G., Rossetti, S., Torres, V. E., & Harris, P. C. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64313 · Cited by 442
Primary cilia as dynamic and diverse signalling hubs in development and disease
Mill, P., Christensen, S. T., & Pedersen, L. B. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00587-9 · Cited by 417
Stages of ciliogenesis and regulation of ciliary length
Avasthi, P., & Marshall, W. F. (2012) · Differentiation · doi:10.1016/j.diff.2011.11.015 · Cited by 234
Primary cilium-dependent signaling mechanisms
Pala, R., Alomari, N., & Nauli, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112272 · Cited by 205
Primary cilia elongation in response to interleukin-1 mediates the inflammatory response
Wann, A. K. T., & Knight, M. M. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0980-y · Cited by 139
Metadata
- Authors
- Besschetnova, T. Y., Kolpakova-Hart, E., Guan, Y., Zhou, J., Olsen, B. R., & Shah, J. V.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 20
- Issue
- 2
- Pages
- 182-187
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2079380806
- Cited by
- 334
- References
- 29
- FWCI
- 13.24
- Type
- journal article
- Language
- en
- Open access
- bronze
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