Conformations, interactions and functions of intrinsically disordered syndecans
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Conformations, interactions and functions of intrinsically disordered syndecans. / Ricard-Blum, Sylvie; Couchman, John R.
In: Biochemical Society Transactions, Vol. 51, No. 3, 2023, p. 1083-1096.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Conformations, interactions and functions of intrinsically disordered syndecans
AU - Ricard-Blum, Sylvie
AU - Couchman, John R.
N1 - Publisher Copyright: © 2023 Portland Press Ltd. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Syndecans are transmembrane heparan sulfate proteoglycans present on most mammalian cell surfaces. They have a long evolutionary history, a single syndecan gene being expressed in bilaterian invertebrates. Syndecans have attracted interest because of their potential roles in development and disease, including vascular diseases, inflammation and various cancers. Recent structural data is providing important insights into their functions, which are complex, involving both intrinsic signaling through cytoplasmic binding partners and co-operative mechanisms where syndecans form a signaling nexus with other receptors such as integrins and tyrosine kinase growth factor receptors. While the cytoplasmic domain of syndecan-4 has a well-defined dimeric structure, the syndecan ectodomains are intrinsically disordered, which is linked to a capacity to interact with multiple partners. However, it remains to fully establish the impact of glycanation and partner proteins on syndecan core protein conformations. Genetic models indicate that a conserved property of syndecans links the cytoskeleton to calcium channels of the transient receptor potential class, compatible with roles as mechanosensors. In turn, syndecans influence actin cytoskeleton organization to impact motility, adhesion and the extracellular matrix environment. Syndecan clustering with other cell surface receptors into signaling microdomains has relevance to tissue differentiation in development, for example in stem cells, but also in disease where syndecan expression can be markedly up-regulated. Since syndecans have potential as diagnostic and prognostic markers as well as possible targets in some forms of cancer, it remains important to unravel structure/function relationships in the four mammalian syndecans.
AB - Syndecans are transmembrane heparan sulfate proteoglycans present on most mammalian cell surfaces. They have a long evolutionary history, a single syndecan gene being expressed in bilaterian invertebrates. Syndecans have attracted interest because of their potential roles in development and disease, including vascular diseases, inflammation and various cancers. Recent structural data is providing important insights into their functions, which are complex, involving both intrinsic signaling through cytoplasmic binding partners and co-operative mechanisms where syndecans form a signaling nexus with other receptors such as integrins and tyrosine kinase growth factor receptors. While the cytoplasmic domain of syndecan-4 has a well-defined dimeric structure, the syndecan ectodomains are intrinsically disordered, which is linked to a capacity to interact with multiple partners. However, it remains to fully establish the impact of glycanation and partner proteins on syndecan core protein conformations. Genetic models indicate that a conserved property of syndecans links the cytoskeleton to calcium channels of the transient receptor potential class, compatible with roles as mechanosensors. In turn, syndecans influence actin cytoskeleton organization to impact motility, adhesion and the extracellular matrix environment. Syndecan clustering with other cell surface receptors into signaling microdomains has relevance to tissue differentiation in development, for example in stem cells, but also in disease where syndecan expression can be markedly up-regulated. Since syndecans have potential as diagnostic and prognostic markers as well as possible targets in some forms of cancer, it remains important to unravel structure/function relationships in the four mammalian syndecans.
U2 - 10.1042/BST20221085
DO - 10.1042/BST20221085
M3 - Review
C2 - 37334846
AN - SCOPUS:85164209771
VL - 51
SP - 1083
EP - 1096
JO - Biochemical Society Transactions
JF - Biochemical Society Transactions
SN - 0300-5127
IS - 3
ER -
ID: 369468857