Localization of the transmembrane proteoglycan syndecan‐4 and its regulatory kinases in costameres of rat cardiomyocytes: A deconvolution microscopic study

  title={Localization of the transmembrane proteoglycan syndecan‐4 and its regulatory kinases in costameres of rat cardiomyocytes: A deconvolution microscopic study},
  author={W Barry VanWinkle and Mark B. Snuggs and Eugenio L. de Hostos and Louis Maximilian Buja and Anne Woods and John R. Couchman},
  journal={The Anatomical Record},
Syndecan‐4 (syn‐4), a transmembrane heparan sulfate‐containing proteoglycan, is unique among the four members of the syndecan family in its specific cellular localization to complex cytoskeletal adhesion sites, i.e., focal adhesions. During early phenotypic redifferentiation of neonatal cardiomyocytes in culture, immunolocalization reveals syn‐4 to be heavily concentrated in the perinuclear endoplasmic reticulum‐Golgi region, with little found at the peripheral regions. Subsequently, syn‐4… 

The cardiac syndecan-4 interactome reveals a role for syndecan-4 in nuclear translocation of muscle LIM protein (MLP)

It is suggested that syndecan-4 mediates nuclear translocation of MLP in the heart and contributes to downstream signaling mechanisms in MLP-mediated signaling.

Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture.

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

The data suggest that syndecan‐4 plays an important role in the immune response of the heart to increased pressure, influencing cardiac remodeling and failure progression.

Syndecan-4 promotes cytokinesis in a phosphorylation-dependent manner

This present work demonstrated that SDC4 promotes cytokinesis in a phosphorylation-dependent manner in MCF-7 breast adenocarcinoma cells and that expression of the phospho-resistant S DC4 led to giant, multinucleated cells.

Roles of Syndecan-4 in Cardiac Injury and Repair.

Protein Kinase C, Focal Adhesions and the Regulation of Cell Migration

The status of protein kinase C in focal adhesions and cell migration is reviewed, together with discussion of its roles and potential substrates.

Helicobacter pylori and toll-like receptor agonists induce syndecan-4 expression in an NF-κB-dependent manner

The response of the syndecan-4 gene to infectious agents, or their products, is a direct result of NF-[kappa]B binding to the promoter and induction of de novo transcription.

The female syndecan-4−/− heart has smaller cardiomyocytes, augmented insulin/pSer473-Akt/pSer9-GSK-3β signaling, and lowered SCOP, pThr308-Akt/Akt and GLUT4 levels

Smaller cardiomyocytes, an elevated insulin/ pSer473-Akt/pSer9-GSK-3β signaling pathway, and lowered SCOP, pThr308-AKT/Akt and GLUT4 levels in the female syndecan-4−/− heart are observed, suggesting important sex differences.



Protein kinase C regulates the recruitment of syndecan-4 into focal contacts.

Investigating the mechanisms regulating the association of syndecan-4 with focal contacts based upon its immunolocalization with vinculin suggests that protein kinase C activation results in syndecans recruitment to focal contacts and its association with sites of matrix deposition.

Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component.

It is reported that syndecan 4 (ryudocan/amphiglycan) is present in focal adhesions of a number of cell types and represents a new transmembrane focal adhesion component, probably involved in their assembly.

Control of morphology, cytoskeleton and migration by syndecan-4.

The data suggest that syndecan-4 is a regulator of focal adhesion and stress fiber formation, and influences both morphology and migration.

Syndecan-4 Proteoglycan Regulates the Distribution and Activity of Protein Kinase C*

It is shown that syndecan-4 transmembrane heparan sulfate proteoglycan and PKC co-immunoprecipitate and co-patch in vivo and represents the first report of direct trans Membrane signaling through cell surface proteoglycans.

Syndecan-4 core protein is sufficient for the assembly of focal adhesions and actin stress fibers.

An essential role is indicated for the core protein of syndecan-4 in the generation of signals leading to actin stress fiber and focal contact assembly in Chinese hamster ovary cells with mutations in key enzymes of the glycanation process.

Syndecan-4-mediated signalling.

Tyrosine Phosphorylation of Syndecan-1 and -4 Cytoplasmic Domains in Adherent B82 Fibroblasts*

Data suggest an important role for tyrosine phosphorylation of the syndecan cytoplasmic domains in regulating downstream signaling events in response to cell adhesion and/or growth factor activity.

Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patterns.

Most, if not all, cells acquire a distinctive repertoire of the four syndecan family members as they differentiate, resulting in selective patterns of expression that likely reflect distinct functions.

Regulation of Syndecan-4 Phosphorylation in Vivo *

It is found that the cytoplasmic tail of syndecan-4 is phosphorylated on a single serine residue (Ser183) in growth-arrested NIH 3T3 fibroblasts, which is regulated by the activities of a novel PKC isozyme and a bFGF-dependent serine/threonine phosphatase.

Syndecan-4 Proteoglycan Cytoplasmic Domain and Phosphatidylinositol 4,5-Bisphosphate Coordinately Regulate Protein Kinase C Activity*

It is indicated that syndecan-4 cytoplasmic domain may bind both PIP2 and PKCα, localize them to forming focal adhesions, and potentiate PKC α activity there.