The Gas7 Gene Encodes Two Protein Isoforms Differentially Expressed within the Brain

Lazakovitch, Elena; She, Bin-Ru; Lien, Ching‐Ling; Woo, Wei‐Meng; Ju, Yu‐Ten; Lin‐Chao, Sue

doi:10.1006/geno.1999.5964

Cited by 21 publications

(30 citation statements)

References 29 publications

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“…Gas7 and N-WASP are strongly expressed in the hippocampus (9, 10, 26, 29). To confirm the correlation between Gas7 and N-WASP in vivo , the localization of Gas7 and N-WASP in the mouse hippocampus was examined.…”

Section: Resultsmentioning

confidence: 99%

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Gas7 Functions with N-WASP to Regulate the Neurite Outgrowth of Hippocampal Neurons

You

Lin‐Chao

2010

Journal of Biological Chemistry

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Neuritogenesis, or neurite outgrowth, is a critical process for neuronal differentiation and maturation in which growth cones are formed from highly dynamic actin structures. Gas7 (growth arrest-specific gene 7), a new member of the PCH (Pombe Cdc15 homology) protein family, is predominantly expressed in neurons and is required for the maturation of primary cultured Purkinje neurons as well as the neuron-like differentiation of PC12 cells upon nerve growth factor stimulation. We report that Gas7 co-localizes and physically interacts with N-WASP, a key regulator of Arp2/3 complex-mediated actin polymerization, in the cortical region of Gas7-transfected Neuro-2a cells and growth cones of hippocampal neurons. The interaction between Gas7 and N-WASP is mediated by WW-Pro domains, which is unique in the PCH protein family, where most interactions are of the SH3-Pro kind. The interaction contributes to the formation of membrane protrusions and processes by recruiting the Arp2/3 complex in a Cdc42-independent manner. Importantly, specific interaction between Gas7 and N-WASP is required for regular neurite outgrowth of hippocampal neurons. The data demonstrate an essential role of Gas7 through its interaction with N-WASP during neuronal maturation/differentiation.

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Section: Resultsmentioning

confidence: 99%

“…Endogenous Gas7- cb is abundant in the nuclei of cerebellar neurons (10). Ectopic expression of Gas7- cb in Neuro-2a cells showed that Gas7- cb is also localized mainly in the nucleus and has no effect on morphological events (supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

Gas7 Functions with N-WASP to Regulate the Neurite Outgrowth of Hippocampal Neurons

You

Lin‐Chao

2010

Journal of Biological Chemistry

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“…Growth arrest-specific gene 7 ( Gas7 ) was discovered in growth-arrested NIH3T3 fibroblasts using a retrovirus-based gene search strategy [1], [2]. Previous studies have shown that Gas7 is expressed in the central nervous system (CNS) including the cerebral cortex, hippocampus, and cerebellum [3].…”

Section: Introductionmentioning

confidence: 99%

Gas7-Deficient Mouse Reveals Roles in Motor Function and Muscle Fiber Composition during Aging

Huang

Chang

et al. 2012

PLoS ONE

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BackgroundGrowth arrest-specific gene 7 (Gas7) has previously been shown to be involved in neurite outgrowth in vitro; however, its actual role has yet to be determined. To investigate the physiological function of Gas7 in vivo, here we generated a Gas7-deficient mouse strain with a labile Gas7 mutant protein whose functions are similar to wild-type Gas7.Methodology/Principal FindingsOur data show that aged Gas7-deficient mice have motor activity defects due to decreases in the number of spinal motor neurons and in muscle strength, of which the latter may be caused by changes in muscle fiber composition as shown in the soleus. In cross sections of the soleus of Gas7-deficient mice, gross morphological features and levels of myosin heavy chain I (MHC I) and MHC II markers revealed significantly fewer fast fibers. In addition, we found that nerve terminal sprouting, which may be associated with slow and fast muscle fiber composition, was considerably reduced at neuromuscular junctions (NMJ) during aging.Conclusions/SignificanceThese findings indicate that Gas7 is involved in motor neuron function associated with muscle strength maintenance.

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“…The Gas7 gene was originally identified in NIH 3T3 cells cultured without serum by using a retrovirus-based gene search strategy (Schneider et al, 1988;Brenner et al, 1989). Orthologs of the Gas7 gene have been identified and cloned from mice, rats, and humans (Ju et al, 1998;Lazakovitch et al, 1999;Chang et al, 2005;Chao et al, 2005). Regardless of the species in which the Gas7 gene was studied, Gas7 genes were shown to encode more than one protein isoform (Ju et al, 1998;Lazakovitch et al, 1999;Chang et al, 2005;Chao et al, 2005).…”

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confidence: 99%

“…Orthologs of the Gas7 gene have been identified and cloned from mice, rats, and humans (Ju et al, 1998;Lazakovitch et al, 1999;Chang et al, 2005;Chao et al, 2005). Regardless of the species in which the Gas7 gene was studied, Gas7 genes were shown to encode more than one protein isoform (Ju et al, 1998;Lazakovitch et al, 1999;Chang et al, 2005;Chao et al, 2005). These isoforms appear to be regulated by various mechanisms, including alternative RNA splicing, different promoters, micro-RNA (miRNA), and alternative translation.…”

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confidence: 99%

Knockdown of growth‐arrest‐specific gene 7b (gas7b) using short‐hairpin RNA desensitizes neuroblastoma cells to cisplatin: Implications for preventing apoptosis of neurons

Hung

Chao

2010

J of Neuroscience Research

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Efficient control of cell survival and cell proliferation is critical for the development of neuron cells. Earlier, we observed that growth arrest-specific gene 7 (Gas7) plays a role in controlling neuritogenesis in mammals. In the present study, we report that the Gas7b isoform is involved in controlling growth arrest and apoptosis of neuroblastoma cells in response to various stimuli. Accordingly, knockdown of Gas7b using small-hairpin RNA (shRNA) was shown to reduce apoptosis induced either by serum starvation or by the antineoplastic agents cisplatin and nocodazole in human neuroblastoma SH-SY5Y cells. Gas7b knockdown also enhanced the ability of the treated cells to form clones in response to cisplatin. On the other hand, forced expression of Gas7a or Gas7b isoform in mouse neuroblastoma Neuro2A cells, which express a defective Gas7 gene, rendered the cells proapoptotic and vulnerable to cisplatin-induced apoptosis. In addition, Neuro2A cells that overexpressed Gas7 showed a reduced ability to form clones. Overexpression of Gas7 produced similar but less extensive effects in nonneuronal HEK293 cells. Taken together, our observations suggest that Gas7b is involved not only in neuritogenesis but also in the regulation of neuronal cell death.

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The Gas7 Gene Encodes Two Protein Isoforms Differentially Expressed within the Brain

Cited by 21 publications

References 29 publications

Gas7 Functions with N-WASP to Regulate the Neurite Outgrowth of Hippocampal Neurons

Gas7 Functions with N-WASP to Regulate the Neurite Outgrowth of Hippocampal Neurons

Gas7-Deficient Mouse Reveals Roles in Motor Function and Muscle Fiber Composition during Aging

Knockdown of growth‐arrest‐specific gene 7b (gas7b) using short‐hairpin RNA desensitizes neuroblastoma cells to cisplatin: Implications for preventing apoptosis of neurons

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