Microtubule nucleation and anchoring at the centrosome are independent processes linked by ninein function

Delgehyr, Nathalie; Sillibourne, James; Bornens, Michel

doi:10.1242/jcs.02302

Cited by 262 publications

(319 citation statements)

References 53 publications

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“…In polarized cells, ninein is also found at noncentrosomal sites, and in neurons it has been implicated in the recapture and stabilization of free MT minus ends as the MTs translocate into developing neurites (Baird et al, 2004). There is evidence that ninein also has a role in MT nucleation and anchoring by providing a direct link between centrioles and ␥-TuRCs (Delgehyr et al, 2005).…”

Section: Generation Of Noncentrosomal Mtsmentioning

confidence: 99%

Generation of noncentrosomal microtubule arrays

Bartolini

Gundersen

2006

Journal of Cell Science

228

219

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In most proliferating and migrating animal cells, the centrosome is the main site for microtubule (MT) nucleation and anchoring, leading to the formation of radial MT arrays in which MT minus ends are anchored at the centrosomes and plus ends extend to the cell periphery. By contrast, in most differentiated animal cell types, including muscle, epithelial and neuronal cells, as well as most fungi and vascular plant cells, MTs are arranged in noncentrosomal arrays that are non-radial. Recent studies suggest that these noncentrosomal MT arrays are generated by a three step process. The initial step involves formation of noncentrosomal MTs by distinct mechanisms depending on cell type: release from the centrosome, catalyzed nucleation at noncentrosomal sites or breakage of pre-existing MTs. The second step involves transport by MT motor proteins or treadmilling to sites of assembly. In the final step, the noncentrosomal MTs are rearranged into cell-type-specific arrays by bundling and/or capture at cortical sites, during which MTs acquire stability. Despite their relative stability, the final noncentrosomal MT arrays may still exhibit dynamic properties and in many cases can be remodeled.

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Section: Generation Of Noncentrosomal Mtsmentioning

confidence: 99%

Generation of noncentrosomal microtubule arrays

Bartolini

Gundersen

2006

Journal of Cell Science

228

219

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“…In line with this, NIN, another gene associated with an SEMD-JL2-like phenotype, 8 encodes ninein required for centrosome maturation and architecture. 18 As building and maintenance of a cilium depend on membrane vesicle trafficking, microtubuledependent motor proteins and formation of basal bodies, 19 we speculate that dysfunction of EXOC6B, KIF22 and ninein negatively affects ciliogenesis leading to overlapping SEMD forms. EXOC6B nonsense variant in a novel SEMD type KM Girisha et al…”

Section: Resultsmentioning

confidence: 91%

A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene

et al. 2015

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We report two brothers from a consanguineous couple with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones, probably representing a yet uncharacterized SEMD with laxity and dislocations. This condition has clinical overlap with autosomal dominantly inherited SEMD with joint laxity, leptodactylic type caused by recurrent missense variants in the kinesin family member 22 gene (KIF22). Single-nucleotide polymorphism array analysis and whole-exome sequencing in the two affected siblings revealed a shared homozygous nonsense variant [c.906T4A/p.(Tyr302*)] in EXOC6B as the most likely cause. EXOC6B encodes a component of the exocyst complex required for tethering secretory vesicles to the plasma membrane. As transport of vesicles from the golgi apparatus to the plasma membrane occurs through kinesin motor proteins along microtubule tracks, the function of EXOC6B is linked to KIF22 suggesting a common pathogenic mechanism in skeletal dysplasias with joint laxity and dislocations. INTRODUCTIONSkeletal dysplasias with multiple joint dislocations is a heterogeneous group of disorders comprising~10 distinct entities. 1 Spondyloepimetaphyseal dysplasia (SEMD) with joint laxity type 2 (leptodactylic type, Hall type or SEMD-JL2; MIM 603546) is an autosomal dominant skeletal dysplasia with short stature, multiple joint dislocations and/or laxity, delayed ossification of carpals, small carpus, severe epiphyseal and mild metaphyseal changes, mild vertebral body deformities and gracile metacarpals. 2 Missense variants affecting one of two amino acids in the motor domain of the kinesin family member KIF22 have been identified to cause SEMD-JL2. 3,4 Key features of SEMD with joint laxity, type 1, with or without fractures (SEMD-JL1; MIM 271640), which is caused by biallelic variants in B3GALT6, 5,6 are joint laxity and dislocations and SEMD. Affected individuals show facial dysmorphism, kyphoscoliosis at birth, talipes equinovarus, cleft palate and congenital heart disease. 7 Another SEMD-JL2-like phenotype is associated with a homozygous missense variant in NIN. 8 Here, we report two brothers with a new type of autosomal recessive SEMD with laxity and joint dislocations. We used single-nucleotide polymorphism (SNP) array analysis and whole-exome sequencing (WES) to identify a homozygous nonsense variant in EXOC6B in the affected siblings.

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“…Thus, as ninein, 14 nucleolin is involved in both microtubule nucleation and anchoring at the centrosome. Nucleolin could anchor microtubules directly or via other anchoring protein localizing at the mature centriole such as ninein 14 since nucleolin antibodies immunoprecipitated ninein, or through p150 glued , APC, FOP, CAP350 and EB1, [40][41][42] Kif3a, 43 nudel 44 or 4.1R-135. 45 Previous studies have shown the presence of extra centrosomes markers containing structure in mitotic cells silenced for nucleolin.…”

Section: Discussionmentioning

confidence: 99%

“…11 The distal appendages are important during ciliogenesis to anchor the mother centriole to the plasma membrane 12,13 whereas the subdistal appendages are involved in microtubule anchoring at the centrosome. 13,14 Even though, proteomic analyzes have identified several proteins associated with the centrosomes, 15,16 their localization within the centrosome structure has only been characterized for a subset of proteins. Development of super-resolution approaches in optics, have recently contributed to decipher internal centrosomal organization.…”

Section: Introductionmentioning

confidence: 99%

“…Even though, it is admitted distinct contributions of g-TuRC and ninein to microtubule nucleation and anchoring processes, it has been proposed that ninein constitutes a molecular link between microtubule-nucleation and -anchoring activities at the centrosome. 14 Nucleolin (NCL) is an abundant non-ribosomal protein of the nucleolus where it is involved in ribosome biogenesis. Nevertheless, nucleolin functions are not restricted to nucleoli as it has been identified in different compartments such as in the nucleoplasm, cytoplasm and at the cell membrane (for review see 27 ).…”

Section: Introductionmentioning

confidence: 99%

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Centrosomal nucleolin is required for microtubule network organization

et al. 2015

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Nucleolin is a pleiotropic protein involved in a variety of cellular processes. Although multipolar spindle formation has been observed after nucleolin depletion, the roles of nucleolin in centrosome regulation and functions have not been addressed. Here we report using immunofluorescence and biochemically purified centrosomes that nucleolin colocalized only with one of the centrioles during interphase which was further identified as the mature centriole. Upon nucleolin depletion, cells exhibited an amplification of immature centriole markers surrounded by irregular pericentrin staining; these structures were exempt from maturation markers and unable to nucleate microtubules. Furthermore, the microtubule network was disorganized in these cells, exhibiting frequent non-centrosomal microtubules. At the mature centriole a reduced kinetics in the centrosomal microtubule nucleation phase was observed in live silenced cells, as well as a perturbation of microtubule anchoring. Immunoprecipitation experiments showed that nucleolin belongs to protein complexes containing 2 key centrosomal proteins, g-tubulin and ninein, involved in microtubule nucleation and anchoring steps. Altogether, our study uncovered a new role for nucleolin in restricting microtubule nucleation and anchoring at centrosomes in interphase cells.

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Microtubule nucleation and anchoring at the centrosome are independent processes linked by ninein function

Abstract: Evidence that an interaction between EB1 and p150 Glued is required for the formation and maintenance of a radial microtubule array anchored at the centrosome. Mol. Biol. Cell 13, 3627-3645.

Cited by 262 publications

References 53 publications

Generation of noncentrosomal microtubule arrays

Generation of noncentrosomal microtubule arrays

A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene

Centrosomal nucleolin is required for microtubule network organization

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