Emerging Roles of Small GTPases in Islet β-Cell Function
Several small guanosine triphosphatases (GTPases) from the Ras protein superfamily regulate glucose-stimulated insulin secretion in the pancreatic islet β-cell. The Rho family GTPases Cdc42 and Rac1 are primarily involved in relaying key signals in several cellular functions, including vesicle traff...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/6/1503 |
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| author | Rajakrishnan Veluthakal Debbie C. Thurmond |
| author_facet | Rajakrishnan Veluthakal Debbie C. Thurmond |
| author_sort | Rajakrishnan Veluthakal |
| collection | DOAJ |
| description | Several small guanosine triphosphatases (GTPases) from the Ras protein superfamily regulate glucose-stimulated insulin secretion in the pancreatic islet β-cell. The Rho family GTPases Cdc42 and Rac1 are primarily involved in relaying key signals in several cellular functions, including vesicle trafficking, plasma membrane homeostasis, and cytoskeletal dynamics. They orchestrate specific changes at each spatiotemporal region within the β-cell by coordinating with signal transducers, guanine nucleotide exchange factors (GEFs), GTPase-activating factors (GAPs), and their effectors. The Arf family of small GTPases is involved in vesicular trafficking (exocytosis and endocytosis) and actin cytoskeletal dynamics. Rab-GTPases regulate pre-exocytotic and late endocytic membrane trafficking events in β-cells. Several additional functions for small GTPases include regulating transcription factor activity and mitochondrial dynamics. Importantly, defects in several of these GTPases have been found associated with type 2 diabetes (T2D) etiology. The purpose of this review is to systematically denote the identities and molecular mechanistic steps in the glucose-stimulated insulin secretion pathway that leads to the normal release of insulin. We will also note newly identified defects in these GTPases and their corresponding regulatory factors (e.g., GDP dissociation inhibitors (GDIs), GEFs, and GAPs) in the pancreatic β-cells, which contribute to the dysregulation of metabolism and the development of T2D. |
| first_indexed | 2024-03-10T10:24:30Z |
| format | Article |
| id | doaj.art-78440518a30b444990c1b02cb40fa3d4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T10:24:30Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-78440518a30b444990c1b02cb40fa3d42023-11-22T00:09:43ZengMDPI AGCells2073-44092021-06-01106150310.3390/cells10061503Emerging Roles of Small GTPases in Islet β-Cell FunctionRajakrishnan Veluthakal0Debbie C. Thurmond1Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope Beckman Research Institute, Duarte, CA 91010, USADepartment of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope Beckman Research Institute, Duarte, CA 91010, USASeveral small guanosine triphosphatases (GTPases) from the Ras protein superfamily regulate glucose-stimulated insulin secretion in the pancreatic islet β-cell. The Rho family GTPases Cdc42 and Rac1 are primarily involved in relaying key signals in several cellular functions, including vesicle trafficking, plasma membrane homeostasis, and cytoskeletal dynamics. They orchestrate specific changes at each spatiotemporal region within the β-cell by coordinating with signal transducers, guanine nucleotide exchange factors (GEFs), GTPase-activating factors (GAPs), and their effectors. The Arf family of small GTPases is involved in vesicular trafficking (exocytosis and endocytosis) and actin cytoskeletal dynamics. Rab-GTPases regulate pre-exocytotic and late endocytic membrane trafficking events in β-cells. Several additional functions for small GTPases include regulating transcription factor activity and mitochondrial dynamics. Importantly, defects in several of these GTPases have been found associated with type 2 diabetes (T2D) etiology. The purpose of this review is to systematically denote the identities and molecular mechanistic steps in the glucose-stimulated insulin secretion pathway that leads to the normal release of insulin. We will also note newly identified defects in these GTPases and their corresponding regulatory factors (e.g., GDP dissociation inhibitors (GDIs), GEFs, and GAPs) in the pancreatic β-cells, which contribute to the dysregulation of metabolism and the development of T2D.https://www.mdpi.com/2073-4409/10/6/1503small GTPaseactin remodelingβ-cellguanine nucleotide exchange factorsreadily releasable poolcytoskeleton |
| spellingShingle | Rajakrishnan Veluthakal Debbie C. Thurmond Emerging Roles of Small GTPases in Islet β-Cell Function Cells small GTPase actin remodeling β-cell guanine nucleotide exchange factors readily releasable pool cytoskeleton |
| title | Emerging Roles of Small GTPases in Islet β-Cell Function |
| title_full | Emerging Roles of Small GTPases in Islet β-Cell Function |
| title_fullStr | Emerging Roles of Small GTPases in Islet β-Cell Function |
| title_full_unstemmed | Emerging Roles of Small GTPases in Islet β-Cell Function |
| title_short | Emerging Roles of Small GTPases in Islet β-Cell Function |
| title_sort | emerging roles of small gtpases in islet β cell function |
| topic | small GTPase actin remodeling β-cell guanine nucleotide exchange factors readily releasable pool cytoskeleton |
| url | https://www.mdpi.com/2073-4409/10/6/1503 |
| work_keys_str_mv | AT rajakrishnanveluthakal emergingrolesofsmallgtpasesinisletbcellfunction AT debbiecthurmond emergingrolesofsmallgtpasesinisletbcellfunction |