The Novel Gene fad158, Having a Transmembrane Domain and Leucine-rich Repeat, Stimulates Adipocyte Differentiation

Tominaga, Kei; Kondo, Chiharu; Kagata, Takeshi; Hishida, Tomoaki; Nishizuka, Makoto; Imagawa, Masayoshi

doi:10.1074/jbc.m312927200

Cited by 43 publications

(37 citation statements)

References 36 publications

(50 reference statements)

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“…LRRC8 proteins also lack a signal peptide and are subjected to glycosylation, at least in the case of LRRC8A and D, the two most widely expressed paralogues [30]. Moreover, LRRC8A and D have been found at the surface of the cell [30] and LRRC8C at the ER [3].…”

Section: Subcellular Localisation Of Lrrc8 Proteins Resembles That Ofmentioning

confidence: 99%

“…immune synapses) would help to clarify whether they are involved in direct or indirect (paracrine) cell-cell communi- cation. Considering the relevant role of pannexins at the ER [61] and that LRRC8C has already been detected at that particular location [3], it would also be important to determine the function of LRRC8 proteins in this organelle. Characterisation of protein-protein interactions, transient or stable, with proteins that participate in signalling cascades and/or cell-cell junctions will also throw light on the function of these proteins.…”

Section: Next Steps In Deciphering the Functions Of Lrrc8 Proteinsmentioning

confidence: 99%

“…Based on the shift in the expression of the lrrc8B gene after stimulation of peripheral blood mononuclear cells, it was proposed that LRRC8B had a role in the activation of lymphocytes and monocytes [2]. The LRRC8C protein was found to be essential for the proper differentiation of adipocytes [3,4]. LRRC8D and E have been less studied, and their functions are unknown.…”

Section: Introductionmentioning

confidence: 99%

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LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

2012

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Leucine-rich repeat-containing 8 (LRRC8) proteins are composed of four transmembrane helices and 17 leucine-rich repeats (LRR). Although LRRC8 proteins have been associated with important processes, like maturation of B cells or adipocyte differentiation, their biology and molecular function are largely unknown. We found that LRRC8 proteins originated from the combination of a pannexin and an LRR domain (most likely related to the SHOC2, LAP, RSU1 and LRRIQ4 protein families) before the diversification of chordates. We propose that, like pannexins, LRRC8 proteins form hexameric channels, which participate in cell-cell communication processes. According to the inferred topological model, and contrary to what was previously assumed, the six LRR domains are located in the cytoplasm, and could participate in the organisation of signalling cascades. By compiling available proteomics and gene expression data, and on the basis of the LRRC8 proposed hexameric channel structure, we present clues to the function of this family.

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Section: Subcellular Localisation Of Lrrc8 Proteins Resembles That Ofmentioning

confidence: 99%

Section: Next Steps In Deciphering the Functions Of Lrrc8 Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

2012

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“…We previously demonstrated that FAD158 localized to the endoplasmic reticulum (ER) through its four N-terminal transmembrane regions. 5) Alteration of the actin cytoskeleton is necessary for early adipocyte differentiation. 25) In addition, Dadke and Chernoff reported that protein-tyrosine phosphatase 1B (PTPIB) localized to the ER, and activated Src, thereby initiating the activation of a Rac-dependent pathway leading to cytoskeletal remodeling.…”

Section: -7)mentioning

confidence: 99%

“…We previously generated stable transformants expressing antisense-TCL/TC10bL and fad158, and described that inhibition of the expression of TCL/TC10bL and fad158 impaired adipogenesis. 4,5) Moreover, using an RNAi method, we found that the knockdown of fad104 expression reduced the ability of 3T3-L1 cells to differentiate. 6) In addition, RGS2-expressing NIH-3T3 cells converted to adipocytes.…”

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confidence: 99%

TC10-Like/TC10.BETA.Long Regulates Adipogenesis by Controlling Mitotic Clonal Expansion

Kawaji

Nishizuka

Osada

et al. 2010

Biological & Pharmaceutical Bulletin

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Obesity is a major health problem in industrialized societies, and is related to the development of type 2 diabetes mellitus, hypertension, and hyperlipidemia. Obesity is thought to occur as a result of hypertrophy of individual adipocytes and hyperplasia of adipocytes.1) Therefore, an understanding of the molecular basis of hyperplasia would contribute to the establishment of medical treatments to prevent the health risks associated with obesity. One explanation for the increase in the number of adipocytes is that preadipocytes in adipose tissue differentiate into mature adipocytes. Therefore, it is important to study the molecular mechanism of adipocyte differentiation.To elucidate the molecular basis of adipocyte differentiation, we previously isolated 102 genes induced to express in the early stages of adipogenesis by a polymerase chain reaction (PCR)-subtraction cloning method.2,3) We identified TC10-like/TC10bLong (TCL/TC10bL), regulators of G protein signaling 2 (RGS2), factor for adipocyte differentiation (fad) 104, and fad158. TCL/TC10bL is a member of the Rho family of small guanosine triphosphatases (GTPases) and RGS2 belongs to a subfamily of small mammalian RGS proteins containing an RGS domain. fad104 and fad158 were identified as novel genes. We previously generated stable transformants expressing antisense-TCL/TC10bL and fad158, and described that inhibition of the expression of TCL/TC10bL and fad158 impaired adipogenesis.4,5) Moreover, using an RNAi method, we found that the knockdown of fad104 expression reduced the ability of 3T3-L1 cells to differentiate.6) In addition, RGS2-expressing NIH-3T3 cells converted to adipocytes. 7) These results strongly indicate that TCL/TC10bL, RGS2, fad104, and fad158 have important roles in adipogenesis. However, their functions in the early phase of adipocyte differentiation have not been addressed.After hormonal induction, growth-arrested 3T3-L1 preadipocytes reenter the cell cycle and undergo several rounds of cell division, referred to as mitotic clonal expansion (MCE). MCE is required for completion of the differentiation program. 8) This step is followed by the terminal differentiated phase in which specific genes defining the adipocyte phenotype are induced to express. [9][10][11] CCAAT/enhancer-binding protein (C/EBP) b and C/EBPd play critical roles in the 3T3-L1 adipocyte differentiation program. Both genes are expressed immediately after hormonal induction, then function as transcriptional activators of the C/EBPa and peroxisome proliferator-activated receptor g (PPARg) genes, both of which serve as pleiotropic transcriptional activators for a large group of adipocyte genes, and induce the terminally differentiated phenotype.12,13) Recent studies have established that C/EBPb is required for MCE during adipocyte differentiation.14,15) In addition, we found that C/EBPd is also required for MCE.16) However, the molecular mechanism of MCE is not fully understood.In this paper, we focused on the roles of TCL/TC10bL, RGS2, fad104, and fad158 during MCE. S...

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Genomic signatures of climate adaptation in bank voles

Folkertsma,

Charbonnel,

Henttonen

et al. 2024

Ecology and Evolution

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Evidence for divergent selection and adaptive variation across the landscape can provide insight into a species' ability to adapt to different environments. However, despite recent advances in genomics, it remains difficult to detect the footprints of climate‐mediated selection in natural populations. Here, we analysed ddRAD sequencing data (21,892 SNPs) in conjunction with geographic climate variation to search for signatures of adaptive differentiation in twelve populations of the bank vole (Clethrionomys glareolus) distributed across Europe. To identify the loci subject to selection associated with climate variation, we applied multiple genotype‐environment association methods, two univariate and one multivariate, and controlled for the effect of population structure. In total, we identified 213 candidate loci for adaptation, 74 of which were located within genes. In particular, we identified signatures of selection in candidate genes with functions related to lipid metabolism and the immune system. Using the results of redundancy analysis, we demonstrated that population history and climate have joint effects on the genetic variation in the pan‐European metapopulation. Furthermore, by examining only candidate loci, we found that annual mean temperature is an important factor shaping adaptive genetic variation in the bank vole. By combining landscape genomic approaches, our study sheds light on genome‐wide adaptive differentiation and the spatial distribution of variants underlying adaptive variation influenced by local climate in bank voles.

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The Novel Gene fad158, Having a Transmembrane Domain and Leucine-rich Repeat, Stimulates Adipocyte Differentiation

Cited by 43 publications

References 36 publications

LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

TC10-Like/TC10.BETA.Long Regulates Adipogenesis by Controlling Mitotic Clonal Expansion

Genomic signatures of climate adaptation in bank voles

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