TY - JOUR

T1 - Proteoglycans, ion channels and cell-matrix adhesion

AU - Mitsou, Ioli

AU - Multhaupt, Hinke A.B.

AU - Couchman, John R.

PY - 2017/6/15

Y1 - 2017/6/15

N2 - Cell surface proteoglycans comprise a transmembrane or membrane-associated core protein to which one or more glycosaminoglycan chains are covalently attached.They are ubiquitous receptors on nearly all animal cell surfaces.In mammals, the cell surface proteoglycans include the six glypicans, CD44, NG2 (CSPG4), neuropilin-1 and four syndecans.A single syndecan is present in invertebrates such as nematodes and insects.Uniquely, syndecans are receptors for many classes of proteins that can bind to the heparan sulphate chains present on syndecan core proteins.These range from cytokines, chemokines, growth factors and morphogens to enzymes and extracellular matrix (ECM) glycoproteins and collagens.Extracellular interactions with other receptors, such as some integrins, are mediated by the core protein.This places syndecans at the nexus of many cellular responses to extracellular cues in development, maintenance, repair and disease.The cytoplasmic domains of syndecans, while having no intrinsic kinase activity, can nevertheless signal through binding proteins.All syndecans appear to be connected to the actin cytoskeleton and can therefore contribute to cell adhesion, notably to the ECM and migration.Recent data now suggest that syndecans can regulate stretchactivated ion channels.The structure and function of the syndecans and the ion channels are reviewed here, along with an analysis of ion channel functions in cell-matrix adhesion.This area sheds new light on the syndecans, not least since evidence suggests that this is an evolutionarily conserved relationship that is also potentially important in the progression of some common diseases where syndecans are implicated.

AB - Cell surface proteoglycans comprise a transmembrane or membrane-associated core protein to which one or more glycosaminoglycan chains are covalently attached.They are ubiquitous receptors on nearly all animal cell surfaces.In mammals, the cell surface proteoglycans include the six glypicans, CD44, NG2 (CSPG4), neuropilin-1 and four syndecans.A single syndecan is present in invertebrates such as nematodes and insects.Uniquely, syndecans are receptors for many classes of proteins that can bind to the heparan sulphate chains present on syndecan core proteins.These range from cytokines, chemokines, growth factors and morphogens to enzymes and extracellular matrix (ECM) glycoproteins and collagens.Extracellular interactions with other receptors, such as some integrins, are mediated by the core protein.This places syndecans at the nexus of many cellular responses to extracellular cues in development, maintenance, repair and disease.The cytoplasmic domains of syndecans, while having no intrinsic kinase activity, can nevertheless signal through binding proteins.All syndecans appear to be connected to the actin cytoskeleton and can therefore contribute to cell adhesion, notably to the ECM and migration.Recent data now suggest that syndecans can regulate stretchactivated ion channels.The structure and function of the syndecans and the ion channels are reviewed here, along with an analysis of ion channel functions in cell-matrix adhesion.This area sheds new light on the syndecans, not least since evidence suggests that this is an evolutionarily conserved relationship that is also potentially important in the progression of some common diseases where syndecans are implicated.

U2 - 10.1042/BCJ20160747

DO - 10.1042/BCJ20160747

M3 - Review

C2 - 28546458

AN - SCOPUS:85020739996

VL - 474

SP - 1965

EP - 1979

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 12

ER -