Structural organization of the human complexin 2 gene (CPLX2) and aspects of its functional activity

Raevskaya, N. M.; Dergunova, Lyudmila V.; Vladychenskaya, Irina P.; Stavchansky, Vasily V.; Oborina, Maria V.; Полтараус, А. Б.; Limborska, Svetlana A.

doi:10.1016/j.gene.2005.07.005

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…Strikingly, Cplx2 variant 1 was downregulated in all stages of differentiation as compared with ISC (Supplementary Figure 6). The two Cplx2 variants also exist in human and rat (Raevskaya et al., 2005) and, although both are associated with bivalent promoters in normal tissue (Supplementary Figure 3), according to our results, they appear to be autonomously regulated during cell differentiation (Supplementary Figure 6). Regarding Cdhr2 , it is of note that its overexpression during differentiation is reversed in most adenomas (Figure 4A), resembling the pattern found in CT26 (Figure 1A) and advanced tumors (see below).…”

Section: Resultssupporting

confidence: 72%

“…The dynamic expression profile is coherent with the participation of many of these genes in the regulation of different functions related with the control of proliferation and cell differentiation. For example, Cplx2 encodes a cytosolic protein involved in the exocytosis of synaptic vesicles (Raevskaya et al., 2005) and the opposite expression pattern of Cplx2 variants could suggest a possible role in the signal transmission required for maintaining the intestinal architecture. Furthermore, Cdhr2 (also known as Protocadherin 24 or pcLKC) overexpression may facilitate cellular polarization (Krahn et al., 2010) and contact inhibition through the β‐Catenin pathway (Ose et al., 2009).…”

Section: Discussionmentioning

confidence: 99%

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Long range epigenetic silencing is a trans‐species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells

et al. 2013

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DNA methylation and chromatin remodeling are frequently implicated in the silencing of genes involved in carcinogenesis. Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types. However, it is unknown whether there is a coordinated regulation of the genes embedded in these regions in normal cells and in early stages of tumor progression. To better characterize the molecular events associated with the regulation and remodeling of these regions we analyzed two regions undergoing LRES in human colon cancer in the mouse model. We demonstrate that LRES also occurs in murine cancer in vivo and mimics the molecular features of the human phenomenon, namely, downregulation of gene expression, acquisition of inactive histone marks, and DNA hypermethylation of specific CpG islands. The genes embedded in these regions showed a dynamic and autonomous regulation during mouse intestinal cell differentiation, indicating that, in the framework considered here, the coordinated regulation in LRES is restricted to cancer. Unexpectedly, benign adenomas in Apc(Min/+) mice showed overexpression of most of the genes affected by LRES in cancer, which suggests that the repressive remodeling of the region is a late event. Chromatin immunoprecipitation analysis of the transcriptional insulator CTCF in mouse colon cancer cells revealed disrupted chromatin domain boundaries as compared with normal cells. Malignant regression of cancer cells by in vitro differentiation resulted in partial reversion of LRES and gain of CTCF binding. We conclude that genes in LRES regions are plastically regulated in cell differentiation and hyperproliferation, but are constrained to a coordinated repression by abolishing boundaries and the autonomous regulation of chromatin domains in cancer cells.

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Section: Resultssupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Long range epigenetic silencing is a trans‐species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells

et al. 2013

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“…Total RNA was isolated from post‐mortem human tissues using an acid‐guanidinium thiocyanate‐phenol‐chloroform method, as described previously (35,36). The investigation was performed following approval from the local Ethics Committee.…”

Section: Methodsmentioning

confidence: 99%

Dynactin Subunit p150Glued Isoforms Notable for Differential Interaction with Microtubules

Zhapparova

Bryantseva

Dergunova

et al. 2009

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Dynactin is a multiprotein complex that enhances dynein activity. The largest dynactin subunit, p150Glued, interacts with microtubules through its N-terminal region that contains a globular cytoskeleton-associated protein (CAP)-Gly domain and basic microtubule-binding domain of unknown structure. The p150Glued gene has a complicated intron-exon structure, and many splice isoforms of p150Glued protein have been predicted. Here we describe novel natural 150 kDa isoforms: the p150Glued-1A isoform, whose basic domain is composed of 41 amino acids, and p150Glued-1B with a basic domain of 21 aa because of the lack of exons 5-7 in the corresponding messenger RNA (mRNA). According to reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot data, p150Glued-1A is expressed in nerve tissues, in cultured cells and in embryonic tissues, while 1B is expressed ubiquitously. Overexpression of GFP-p150Glued-1A and -1B fusion proteins and immunostaining of cultured cells with 1A-specific antibodies show that the p150Glued-1A isoform is distributed along microtubules, whereas 1B is associated with microtubule plus-ends. The higher affinity of the p150Glued-1A isoform for microtubules is confirmed by a co-pelleting assay. In fibroblast-like cells, the interaction of p150Glued-1A with microtubules is less dependent on EB1/EB3 and CLIP170 proteins, compared with p150Glued-1B. In polarized cells, p150Glued-1A decorates microtubules that face the leading edge of the cell. The pattern of p150Glued-1A and p150Glued-1B interaction with microtubules and their tissue-specific expression patterns suggest that these isoforms might be involved in cell differentiation and proliferation.

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“…The two rat isoforms each contain 134 amino acid residues and are 86% identical. The corresponding murine and human gene structures are similar (8,27), and at the protein level, complexin-2 is completely conserved in several mammalian species and complexin-1 protein sequences differ only marginally between mice and humans (97% identity) (22,23). (11,22).…”

Section: The Complexin Protein Familymentioning

confidence: 96%

For Better or for Worse: Complexins Regulate SNARE Function and Vesicle Fusion

Brose

2008

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In contrast to constitutive secretion, SNARE-mediated synaptic vesicle fusion is controlled by multiple regulatory proteins, which determine the Ca 21 sensitivity of the vesicle fusion process and the speed of excitation-secretion coupling. Complexins are among the best characterized SNARE regulators known to date. They operate by binding to trimeric SNARE complexes consisting of the vesicle protein synaptobrevin and the plasma membrane proteins syntaxin and SNAP-25. The question as to whether complexins facilitate or inhibit SNARE-mediated fusion processes is currently a matter of significant controversy. This is mainly because of the fact that biochemical experiments in vitro and studies on vertebrate complexins in vivo have yielded apparently contradictory results. In this review, I provide a summary of available data on the role of complexins in SNARE-mediated vesicle fusion and attempt to define a model of complexin function that incorporates evidence for both facilitatory and inhibitory roles of complexins in SNARE-mediated fusion.

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Structural organization of the human complexin 2 gene (CPLX2) and aspects of its functional activity

Cited by 8 publications

References 35 publications

Long range epigenetic silencing is a trans‐species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells

Long range epigenetic silencing is a trans‐species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells

Dynactin Subunit p150Glued Isoforms Notable for Differential Interaction with Microtubules

For Better or for Worse: Complexins Regulate SNARE Function and Vesicle Fusion

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