Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

Espigat-Georger, Aude; Dyachuk, Vyacheslav; Chemin, Cécile; Emorine, Laurent J.; Merdes, Andreas

doi:10.1242/dev.146878

Cited by 19 publications

(23 citation statements)

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“…Second, the association of rootletin with the NE suggests additional in vivo functions for rootletin beyond ciliary rootlets. To that respect, Espigat-Georger and colleagues recently reported that Nesprin1 is essential for the NE relocalization of centrosomal proteins such as PCM-1 during myoblasts differentiation [44]. Finally, our RT-PCR experiments in photoreceptors indicating that rootlet-associated Nesprin1α may harbor a KASH domain (Figure 1E and S1E, F) and the recruitment of all endogenous LINC complex components at Myc-Root centrosomes (Figure 3 A–D) suggest the provocative hypothesis that SUN/KASH interactions may actually take place beyond the NE in specific physiological settings.…”

Section: Resultsmentioning

confidence: 99%

Multiple Isoforms of Nesprin1 Are Integral Components of Ciliary Rootlets

et al. 2017

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SUMMARY SYNE1 (Synaptic nuclear envelope 1) encodes multiple isoforms of Nesprin1 (Nuclear Envelope Spectrin 1) that associate with the nuclear envelope (NE) through a C-terminal KASH (Klarsicht/Anc1/Syne homology) domain (Figure 1A) [1–4]. This domain interacts directly with the SUN (Sad1/Unc84) domain of Sun proteins [5–7], a family of transmembrane proteins of the inner nuclear membrane (INM) [8, 9], to form the so-called LINC complexes (Linkers of the Nucleoskeleton and the Cytoskeleton) that span the whole NE and mediate nuclear positioning [10–12]. In a stark departure from this classical depiction of Nesprin1 in the context of the NE, we report that rootletin recruits Nesprin1α at the ciliary rootlets of photoreceptors and identified asymmetric NE aggregates of Nesprin1α and Sun2 that dock filaments of rootletin at the nuclear surface. In NIH3t3 cells, we show that recombinant rootletin filaments also dock to the NE through the specific recruitment of a ~600 kDa endogenous isoform of Nesprin1 (Nes1600kDa) and of Sun2. In agreement with the association of Nesprin1α with photoreceptor ciliary rootlets and the functional interaction between rootletin and Nesprin1 in fibroblasts, we demonstrate that multiple isoforms of Nesprin1 are integral components of ciliary rootlets of multiciliated ependymal and tracheal cells. Together, these data provide a novel functional paradigm for Nesprin1 at ciliary rootlets and suggest that the wide spectrum of human pathologies linked to truncating mutations of SYNE1 [13–15] may in part originate from ciliary defects.

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Section: Resultsmentioning

confidence: 99%

Multiple Isoforms of Nesprin1 Are Integral Components of Ciliary Rootlets

et al. 2017

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“…Centriolar satellites are electron-dense, microtubule-associated, membraneless granules of~70-100 nm that surround the centrosome and the basal body of the primary cilium (Bernhard & de Harven, 1960;de Thé, 1964;Sorokin, 1968;Steinman, 1968;Anderson & Brenner, 1971). Centriolar satellites have been observed both in proliferating and differentiated cells (Dammermann & Merdes, 2002;Vladar & Stearns, 2007;Espigat-Georger et al, 2016;Wang et al, 2016). The large coiled-coil protein Pericentriolar Material 1 (PCM1) was the first centriolar satellite constituent identified (Balczon et al, 1994;Kubo et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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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“…In dividing cells, the protein pericentriolar material 1 (PCM1) is associated with the centrosome where it is important for microtubule organization and centrosome proteostasis . In differentiated post‐mitotic myocytes, the protein relocalizes to the nuclear envelope where it forms an insoluble matrix . As myonuclei are in a post‐mitotic state, PCM1 is found on the nuclear envelope in adult skeletal muscle .…”

Section: Introductionmentioning

confidence: 99%