Heparan sulfate chain valency controls syndecan-4 function in cell adhesion
(2010) In The Journal of biological chemistry 285(19). p.14247-14258- Abstract
Fibroblasts null for the transmembrane proteoglycan, syndecan-4, have an altered actin cytoskeleton, compared with matching wild-type cells. They do not organize alpha-smooth muscle actin into bundles, but will do so when full-length syndecan-4 is re-expressed. This requires the central V region of the core protein cytoplasmic domain, though not interactions with PDZ proteins. A second key requirement is multiple heparan sulfate chains. Mutant syndecan-4 with no chains, or only one chain, failed to restore the wild-type phenotype, whereas those expressing two or three were competent. However, clustering of one-chain syndecan-4 forms with antibodies overcame the block, indicating that valency of interactions with ligands is a key... (More)
Fibroblasts null for the transmembrane proteoglycan, syndecan-4, have an altered actin cytoskeleton, compared with matching wild-type cells. They do not organize alpha-smooth muscle actin into bundles, but will do so when full-length syndecan-4 is re-expressed. This requires the central V region of the core protein cytoplasmic domain, though not interactions with PDZ proteins. A second key requirement is multiple heparan sulfate chains. Mutant syndecan-4 with no chains, or only one chain, failed to restore the wild-type phenotype, whereas those expressing two or three were competent. However, clustering of one-chain syndecan-4 forms with antibodies overcame the block, indicating that valency of interactions with ligands is a key component of syndecan-4 function. Measurements of focal contact/adhesion size and focal adhesion kinase phosphorylation correlated with syndecan-4 status and alpha-smooth muscle actin organization, being reduced where syndecan-4 function was compromised by a lack of multiple heparan sulfate chains.
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- author
- Gopal, Sandeep LU ; Bober, Adam ; Whiteford, James R ; Multhaupt, Hinke A B ; Yoneda, Atsuko and Couchman, John R
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- keywords
- Actins/metabolism, Amino Acid Sequence, Animals, Blotting, Western, COS Cells, Cell Adhesion, Cells, Cultured, Chlorocebus aethiops, Cytoskeleton/metabolism, Embryo, Mammalian/cytology, Fibroblasts/metabolism, Fibronectins/metabolism, Focal Adhesion Protein-Tyrosine Kinases/metabolism, Heparitin Sulfate/physiology, Humans, Mice, Mice, Knockout, Microscopy, Fluorescence, Molecular Sequence Data, Phosphorylation, Proteoglycans/metabolism, Syndecan-4/physiology
- in
- The Journal of biological chemistry
- volume
- 285
- issue
- 19
- pages
- 14247 - 14258
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:20154082
- scopus:77951994425
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M109.056945
- language
- English
- LU publication?
- no
- id
- 32e4920a-5532-48da-9fde-178e8f6248ad
- date added to LUP
- 2021-10-25 13:22:34
- date last changed
- 2024-10-06 07:46:36
@article{32e4920a-5532-48da-9fde-178e8f6248ad, abstract = {{<p>Fibroblasts null for the transmembrane proteoglycan, syndecan-4, have an altered actin cytoskeleton, compared with matching wild-type cells. They do not organize alpha-smooth muscle actin into bundles, but will do so when full-length syndecan-4 is re-expressed. This requires the central V region of the core protein cytoplasmic domain, though not interactions with PDZ proteins. A second key requirement is multiple heparan sulfate chains. Mutant syndecan-4 with no chains, or only one chain, failed to restore the wild-type phenotype, whereas those expressing two or three were competent. However, clustering of one-chain syndecan-4 forms with antibodies overcame the block, indicating that valency of interactions with ligands is a key component of syndecan-4 function. Measurements of focal contact/adhesion size and focal adhesion kinase phosphorylation correlated with syndecan-4 status and alpha-smooth muscle actin organization, being reduced where syndecan-4 function was compromised by a lack of multiple heparan sulfate chains.</p>}}, author = {{Gopal, Sandeep and Bober, Adam and Whiteford, James R and Multhaupt, Hinke A B and Yoneda, Atsuko and Couchman, John R}}, issn = {{1083-351X}}, keywords = {{Actins/metabolism; Amino Acid Sequence; Animals; Blotting, Western; COS Cells; Cell Adhesion; Cells, Cultured; Chlorocebus aethiops; Cytoskeleton/metabolism; Embryo, Mammalian/cytology; Fibroblasts/metabolism; Fibronectins/metabolism; Focal Adhesion Protein-Tyrosine Kinases/metabolism; Heparitin Sulfate/physiology; Humans; Mice; Mice, Knockout; Microscopy, Fluorescence; Molecular Sequence Data; Phosphorylation; Proteoglycans/metabolism; Syndecan-4/physiology}}, language = {{eng}}, number = {{19}}, pages = {{14247--14258}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{The Journal of biological chemistry}}, title = {{Heparan sulfate chain valency controls syndecan-4 function in cell adhesion}}, url = {{http://dx.doi.org/10.1074/jbc.M109.056945}}, doi = {{10.1074/jbc.M109.056945}}, volume = {{285}}, year = {{2010}}, }