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Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance

Our previous studies demonstrated that collapsin response mediator protein 2 (CRMP2) is associated with obesity and, in addition, that hyperglycemia-suppressed CRMP2 augments malignant traits of colorectal cancer and is associated with advanced tumor stage. Regulation of CRMP2 profile was further ex...

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Autores principales: Chang, Yih-Hsin, Chang, Shu-Wen, Hsu, Wei-Ting, Yang, Ching-Ping, Lo, Yu-Li, Chen, Chun-Jung, Tsai, Hui-Fang, Shiau, Ming-Yuh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599587/
https://www.ncbi.nlm.nih.gov/pubmed/36289868
http://dx.doi.org/10.3390/biomedicines10102603
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author Chang, Yih-Hsin
Chang, Shu-Wen
Hsu, Wei-Ting
Yang, Ching-Ping
Lo, Yu-Li
Chen, Chun-Jung
Tsai, Hui-Fang
Shiau, Ming-Yuh
author_facet Chang, Yih-Hsin
Chang, Shu-Wen
Hsu, Wei-Ting
Yang, Ching-Ping
Lo, Yu-Li
Chen, Chun-Jung
Tsai, Hui-Fang
Shiau, Ming-Yuh
author_sort Chang, Yih-Hsin
collection PubMed
description Our previous studies demonstrated that collapsin response mediator protein 2 (CRMP2) is associated with obesity and, in addition, that hyperglycemia-suppressed CRMP2 augments malignant traits of colorectal cancer and is associated with advanced tumor stage. Regulation of CRMP2 profile was further explored in this study using 3T3-L1 pre-adipocyte adipogenesis as a study model for illustrating the roles of CRMP2 in metabolic homeostasis. Hyperglycemia inhibited expression of CRMP2, adipogenic machinery and adipocyte markers. CRMP2 displayed f-CRMP2 (62~66 kDa) and s-CMRP2 (58 kDa) isoforms at the growth arrest phase. Expression of s-CRMP2 was coupled with the mitotic clonal expansion (MCE) phase to direct cell proliferation and rapidly down-regulated in post-mitotic cells. In the late differentiation phase, f-CRMP2 was co-localized with tubulin in the cortical area. Insulin-enhanced CRMP2-glucose transporter 4 (GLUT4) co-localization and CRMP2 puncta on lipid droplets (LDs) suggested participation of CRMP2 in GLUT4 translocation and LD fusion. Collectively, the CRMP2 functional profile must be finely controlled to adjust cytoskeletal stability for meeting dynamic cellular needs. Manipulating the s-CRMP2/f-CRMP2 ratio and thus the cytoskeleton dynamics is anticipated to improve glucose uptake and insulin sensitivity. In summary, our data provide molecular evidence explaining the functions of CRMP2 in physiological, pathological and disease progression in metabolic homeostasis and disorders related to metabolic abnormalities, including cancer.
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spelling pubmed-95995872022-10-27 Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance Chang, Yih-Hsin Chang, Shu-Wen Hsu, Wei-Ting Yang, Ching-Ping Lo, Yu-Li Chen, Chun-Jung Tsai, Hui-Fang Shiau, Ming-Yuh Biomedicines Article Our previous studies demonstrated that collapsin response mediator protein 2 (CRMP2) is associated with obesity and, in addition, that hyperglycemia-suppressed CRMP2 augments malignant traits of colorectal cancer and is associated with advanced tumor stage. Regulation of CRMP2 profile was further explored in this study using 3T3-L1 pre-adipocyte adipogenesis as a study model for illustrating the roles of CRMP2 in metabolic homeostasis. Hyperglycemia inhibited expression of CRMP2, adipogenic machinery and adipocyte markers. CRMP2 displayed f-CRMP2 (62~66 kDa) and s-CMRP2 (58 kDa) isoforms at the growth arrest phase. Expression of s-CRMP2 was coupled with the mitotic clonal expansion (MCE) phase to direct cell proliferation and rapidly down-regulated in post-mitotic cells. In the late differentiation phase, f-CRMP2 was co-localized with tubulin in the cortical area. Insulin-enhanced CRMP2-glucose transporter 4 (GLUT4) co-localization and CRMP2 puncta on lipid droplets (LDs) suggested participation of CRMP2 in GLUT4 translocation and LD fusion. Collectively, the CRMP2 functional profile must be finely controlled to adjust cytoskeletal stability for meeting dynamic cellular needs. Manipulating the s-CRMP2/f-CRMP2 ratio and thus the cytoskeleton dynamics is anticipated to improve glucose uptake and insulin sensitivity. In summary, our data provide molecular evidence explaining the functions of CRMP2 in physiological, pathological and disease progression in metabolic homeostasis and disorders related to metabolic abnormalities, including cancer. MDPI 2022-10-17 /pmc/articles/PMC9599587/ /pubmed/36289868 http://dx.doi.org/10.3390/biomedicines10102603 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Yih-Hsin
Chang, Shu-Wen
Hsu, Wei-Ting
Yang, Ching-Ping
Lo, Yu-Li
Chen, Chun-Jung
Tsai, Hui-Fang
Shiau, Ming-Yuh
Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance
title Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance
title_full Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance
title_fullStr Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance
title_full_unstemmed Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance
title_short Implication of Adipogenesis-Coupled CRMP2 Functional Profile in Metabolic Homeostasis and Imbalance
title_sort implication of adipogenesis-coupled crmp2 functional profile in metabolic homeostasis and imbalance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599587/
https://www.ncbi.nlm.nih.gov/pubmed/36289868
http://dx.doi.org/10.3390/biomedicines10102603
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