SUN1/2 and Syne/Nesprin-1/2 Complexes Connect Centrosome to the Nucleus during Neurogenesis and Neuronal Migration in Mice

Zhang, Xiaochang; Lei, Kai Y.; Yuan, Xiao-bing; Wu, Xiaohui; Zhuang, Yuan; Xu, Tian; Xu, Rener; Han, Min

doi:10.1016/j.neuron.2009.08.018

Cited by 413 publications

(518 citation statements)

References 64 publications

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“…Freshly dissected eyes were enucleated and two eye cups were homogenized in 200 µl TNP buffer [48] to make retina protein extracts. Preparation of cell lysates from other tissues, co-immunoprecipitation and western blot analyses with antibodies against DIC, DHC, and DLIC1 were performed according to the procedures described previously [48].…”

Section: Immunoprecipitation and Western Blot Analysesmentioning

confidence: 99%

“…Preparation of cell lysates from other tissues, co-immunoprecipitation and western blot analyses with antibodies against DIC, DHC, and DLIC1 were performed according to the procedures described previously [48]. For quantification of protein levels, appropriate film exposures were scanned, the density of bands were determined with image J and normalized to band intensity for GAPDH.…”

Section: Immunoprecipitation and Western Blot Analysesmentioning

confidence: 99%

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Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Kong

Peng

et al. 2013

Cell Res

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Cytoplasmic dynein 1 is fundamentally important for transporting a variety of essential cargoes along microtubules within eukaryotic cells. However, in mammals, few mutants are available for studying the effects of defects in dynein-controlled processes in the context of the whole organism. Here, we deleted mouse Dlic1 gene encoding DLIC1, a subunit of the dynein complex. Dlic1 −/− mice are viable, but display severe photoreceptor degeneration. Ablation of Dlic1 results in ectopic accumulation of outer segment (OS) proteins, and impairs OS growth and ciliogenesis of photoreceptors by interfering with Rab11-vesicle trafficking and blocking efficient OS protein transport from Golgi to the basal body. Our studies show that Dlic1 deficiency partially blocks vesicle export from endoplasmic reticulum (ER), but seems not to affect vesicle transport from the ER to Golgi. Further mechanistic study reveals that lack of Dlic1 destabilizes dynein subunits and alters the normal subcellular distribution of dynein in photoreceptors, probably due to the impaired transport function of dynein. Our results demonstrate that Dlic1 plays important roles in ciliogenesis and protein transport to the OS, and is required for photoreceptor development and survival. The Dlic1 −/− mice also provide a new mouse model to study human retinal degeneration.

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Section: Immunoprecipitation and Western Blot Analysesmentioning

confidence: 99%

Section: Immunoprecipitation and Western Blot Analysesmentioning

confidence: 99%

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Kong

Peng

et al. 2013

Cell Res

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“…Experiments in knockout mice revealed that the SUN-domain proteins SUN1 and SUN2 and the KASHdomain proteins Syne-1/Nesprin-1 and Syne-2/Nesprin-2 play an important role in regulating interkinetic nuclear migration as well as neuronal migration in mice. Syne-2 is connected to the centrosome through interactions with both dynein/dynactin and kinesin complexes (Zhang et al 2009). It is likely that as they mediate the microtubule binding to the nucleus, that they serve as transducers of the forces applied to them by the motors to the nucleus (Fig.…”

Section: Molecular Motors and The Cytoskeletonmentioning

confidence: 99%

Interkinetic Nuclear Movement in the Ventricular Zone of the Cortex

2011

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The nuclei of neuroepithelial cells move along the apicobasal axis in synchronization with their cell cycle status. This motility is known as interkinetic nuclear movement. We discuss here the importance of cytoskeleton organization, the centrosome, molecular motors, cell polarity proteins, and their regulators in controlling and maintaining this typical behavior. Furthermore, due to the tight linkage between cell proliferation, cell cycle, and nuclear motility, we speculate that interkinetic nuclear movement is likely to be affected in the pathophysiology of microcephaly, where the brain size is markedly reduced.

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“…These defects resulted from a depletion of neural progenitor cells. Nesprin-2 is thought to couple the LINC complex to the centrosome and this link has an impact on the crucial functions of the centrosome during brain development [16,26]. The loss of KASH-domain containing Syne 2 isoforms also affected nuclear migration in photoreceptor cells and caused a reduced thickness of the outer nuclear layer in the eye[27].…”

Section: Introductionmentioning

confidence: 99%

Depletion of Nesprin-2 is associated with an embryonic lethal phenotype in mice

Mroß

Marko

Munck

et al. 2018

Nucleus

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Nesprin-2 is a nuclear envelope component and provides a link between cytoskeletal components of the cytoplasm and the nucleoplasm. Several isoforms are generated from its gene Syne2. Loss of the largest isoform Nesprin-2 Giant in mice is associated with a skin phenotype and altered wound healing, loss of C-terminal isoforms in mice leads to cardiomyopathies and neurological defects. Here we attempted to establish mice with an inducible knockout of all Nesprin-2 isoforms by inserting shRNA encoding sequences targeting the N- and C-terminus into the ROSA26 locus of mice. This caused early embryonic death of the animals harboring the mutant allele, which was presumably due to leaky expression of the shRNAs. Mutant embryos were only observed before E13. They had an altered appearance and were smaller in size than their wild type littermates. From this we conclude that the Nesprin-2 gene function is crucial during embryonic growth, differentiation and organogenesis.

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SUN1/2 and Syne/Nesprin-1/2 Complexes Connect Centrosome to the Nucleus during Neurogenesis and Neuronal Migration in Mice

Cited by 413 publications

References 64 publications

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Interkinetic Nuclear Movement in the Ventricular Zone of the Cortex

Depletion of Nesprin-2 is associated with an embryonic lethal phenotype in mice

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