TY - JOUR

T1 - Syndecans – key regulators of cell signaling and biological functions

AU - Afratis, Nikolaos A.

AU - Nikitovic, Dragana

AU - Multhaupt, Hinke A.B.

AU - Theocharis, Achilleas D.

AU - Couchman, John R.

AU - Karamanos, Nikos K.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Syndecans are a small family of four transmembrane proteoglycans in mammals. They have similar structural organization, consisting of an N-terminal ectodomain, single transmembrane domain and C-terminal cytoplasmic domain. Over the years, the association between syndecans and the actin cytoskeleton has been established, which has consequences for the regulation of cell adhesion and migration. Specifically, ecto- and cytoplasmic domains are responsible for the interaction with extracellular matrix molecules and intracellular kinases, respectively. These interactions indicate syndecans as key molecules during cancer initiation and progression. Particularly syndecans interact with other cell surface receptors, such as growth factor receptors and integrins, which lead to activation of downstream signaling pathways, which are critical for the cellular behavior. Moreover, this review describes the key role of syndecans in intracellular calcium regulation and homeostasis. The syndecan-mediated regulation of calcium metabolism is highly correlated with cells’ adhesion phenotype through the actin cytoskeleton and formation of junctions, with implications during differentiation and disease progression.

AB - Syndecans are a small family of four transmembrane proteoglycans in mammals. They have similar structural organization, consisting of an N-terminal ectodomain, single transmembrane domain and C-terminal cytoplasmic domain. Over the years, the association between syndecans and the actin cytoskeleton has been established, which has consequences for the regulation of cell adhesion and migration. Specifically, ecto- and cytoplasmic domains are responsible for the interaction with extracellular matrix molecules and intracellular kinases, respectively. These interactions indicate syndecans as key molecules during cancer initiation and progression. Particularly syndecans interact with other cell surface receptors, such as growth factor receptors and integrins, which lead to activation of downstream signaling pathways, which are critical for the cellular behavior. Moreover, this review describes the key role of syndecans in intracellular calcium regulation and homeostasis. The syndecan-mediated regulation of calcium metabolism is highly correlated with cells’ adhesion phenotype through the actin cytoskeleton and formation of junctions, with implications during differentiation and disease progression.

KW - cell adhesion

KW - growth factor receptors

KW - growth factors

KW - integrins

KW - migration

KW - signaling

KW - syndecans

U2 - 10.1111/febs.13940

DO - 10.1111/febs.13940

M3 - Review

C2 - 27790852

AN - SCOPUS:85003935965

VL - 284

SP - 27

EP - 41

JO - F E B S Journal

JF - F E B S Journal

SN - 1742-464X

IS - 1

ER -