Primary cilia: Cell and molecular mechanosensors directing whole tissue function

Spasic, Milos; Jacobs, Christopher R.

doi:10.1016/j.semcdb.2017.08.036

Cited by 85 publications

(75 citation statements)

References 113 publications

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“…Conversion of the mother centriole into a basal body underscores cilium assembly; distal and subdistal appendages facilitate recruitment of Golgi-derived vesicles onto the distal end of the mother centriole, which enable fusion with the plasma membrane and subsequent axoneme extension (Vertii et al, 2016). Consistent with the role of primary cilia in coordinating several signal transduction pathways including Hedgehog and PDGFR, cilia defects manifest as multisystemic genetic disorders and diseases (Spasic & Jacobs, 2017;Wang & Dynlacht, 2018).…”

Section: Introductionmentioning

confidence: 97%

“…In animal cells, the centrosome fulfils at least two distinct roles: in proliferating cells, it acts as the dominant microtubule-organising centre, whereas in non-dividing cells, it enables formation of the primary cilium, a sensory organelle that transduces chemical and mechanical signals (Spasic & Jacobs, 2017). Both these roles rely on tight control of centrosome numbers, achieved by a cell cycle-coupled centrosome assembly pathway (Banterle & Gonczy, 2017;Nigg & Holland, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Centriolar satellites are acentriolar assemblies of centrosomal proteins

et al. 2019

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Centrioles are core structural elements of both centrosomes and cilia. Although cytoplasmic granules called centriolar satellites have been observed around these structures, lack of a comprehensive inventory of satellite proteins impedes our understanding of their ancestry. To address this, we performed mass spectrometry (MS)‐based proteome profiling of centriolar satellites obtained by affinity purification of their key constituent, PCM1, from sucrose gradient fractions. We defined an interactome consisting of 223 proteins, which showed striking enrichment in centrosome components. The proteome also contained new structural and regulatory factors with roles in ciliogenesis. Quantitative MS on whole‐cell and centriolar satellite proteomes of acentriolar cells was performed to reveal dependencies of satellite composition on intact centrosomes. Although most components remained associated with PCM1 in acentriolar cells, reduced cytoplasmic and satellite levels were observed for a subset of centrosomal proteins. These results demonstrate that centriolar satellites and centrosomes form independently but share a substantial fraction of their proteomes. Dynamic exchange of proteins between these organelles could facilitate their adaptation to changing cellular environments during development, stress response and tissue homeostasis.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Centriolar satellites are acentriolar assemblies of centrosomal proteins

et al. 2019

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“…Primary cilia are involved in numerous other signalling pathways, including the Wnt/PCP (planar cell polarity), Notch and TGF-β pathways, and may thus serve to integrate multiple signals to ensure an appropriate cellular response [39, 46–48]. The primary cilia of some cells, such as renal tubule epithelial cells, are thought to sense fluid flow via mechanosensitive calcium channel complexes within the ciliary membrane [49]. However, this aspect of cilia function has been questioned by recent data [49, 50].…”

Section: Introductionmentioning

confidence: 99%

“…The primary cilia of some cells, such as renal tubule epithelial cells, are thought to sense fluid flow via mechanosensitive calcium channel complexes within the ciliary membrane [49]. However, this aspect of cilia function has been questioned by recent data [49, 50]. …”

Section: Introductionmentioning

confidence: 99%

ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits

Hearn

2018

J Mol Med

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Alström syndrome (AS) is characterised by metabolic deficits, retinal dystrophy, sensorineural hearing loss, dilated cardiomyopathy and multi-organ fibrosis. Elucidating the function of the mutated gene, ALMS1, is critical for the development of specific treatments and may uncover pathways relevant to a range of other disorders including common forms of obesity and type 2 diabetes. Interest in ALMS1 is heightened by the recent discovery of its involvement in neonatal cardiomyocyte cell cycle arrest, a process with potential relevance to regenerative medicine. ALMS1 encodes a ~ 0.5 megadalton protein that localises to the base of centrioles. Some studies have suggested a role for this protein in maintaining centriole-nucleated sensory organelles termed primary cilia, and AS is now considered to belong to the growing class of human genetic disorders linked to ciliary dysfunction (ciliopathies). However, mechanistic details are lacking, and recent studies have implicated ALMS1 in several processes including endosomal trafficking, actin organisation, maintenance of centrosome cohesion and transcription. In line with a more complex picture, multiple isoforms of the protein likely exist and non-centrosomal sites of localisation have been reported. This review outlines the evidence for both ciliary and extra-ciliary functions of ALMS1.

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“…Cilia are slender, microscopic, hair-like microtubulebased structures emanating from the surface of most eukaryotic cells that act as organelles for motility and sensation. Based on their function, cilia are categorized into two types, i.e., motile cilia that have a rhythmic waving motion mediating fluid flow in the extracellular milieu, and non-motile or primary cilia that act as cell's antenna and harbor many sensory receptors and signaling molecules (Spasic and Jacobs, 2017). Primary cilia regulate transduction of various signaling pathways, such as Sonic hedgehog (Shh), Wnt and Platelet-derived growth factor (PDGF), which are Arl11 exhibit nucleo-cytoplasmic distribution and can also be found on cortical actin structures and regulates ERK1/2 signaling.…”

Section: Arls In Cilia and Ciliogenesismentioning

confidence: 99%

Emerging roles of Arl GTPases in regulating cellular functions

Sharma

Marwaha

Dwivedi

2019

PINSA

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Members of Rab and ADP-ribosylation factor (Arf) family of small GTP-binding (G) proteins regulate several aspects of intracellular transport and cytoskeleton organization. The phylogenetic analysis, combined with database mining approaches has led to the identification of Arf-like (Arl) G proteins as a sub-group of the Arf family with approximately 20 members in mammals. Arls are similar in structure to the Arfs, but exhibit immense diversity pertaining to their mechanisms of membrane recruitment, subcellular distribution and cellular functions. Only a few members of this sub-group are currently characterized, while information on the majority of Arl proteins remains scanty or is not known. In this review, we will cover our current understanding of the functions performed by Arl sub-family members, described under three broad categories: Arls involved in primary cilia formation and function, Arls engaged in secretory and endocytic transport, and Arls regulating microtubule and actin organization.

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Primary cilia: Cell and molecular mechanosensors directing whole tissue function

Cited by 85 publications

References 113 publications

Centriolar satellites are acentriolar assemblies of centrosomal proteins

Centriolar satellites are acentriolar assemblies of centrosomal proteins

ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits

Emerging roles of Arl GTPases in regulating cellular functions

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