Fell-Muir Lecture : Syndecans: from peripheral coreceptors to mainstream regulators of cell behaviour
Couchman, John R ; Gopal, Sandeep LU
; Lim, Hooi Ching
LU
; Nørgaard, Steffen
and Multhaupt, Hinke A B
(2015)
In International Journal of Experimental Pathology
96(1).
p.1-10
- Abstract
In the 25 years, as the first of the syndecan family was cloned, interest in these transmembrane proteoglycans has steadily increased. While four distinct members are present in mammals, one is present in invertebrates, including C. elegans that is such a powerful genetic model. The syndecans, therefore, have a long evolutionary history, indicative of important roles. However, these roles have been elusive. The knockout in the worm has a developmental neuronal phenotype, while knockouts of the syndecans in the mouse are mild and mostly limited to post-natal rather than developmental effects. Moreover, their association with high-affinity receptors, such as integrins, growth factor receptors, frizzled and slit/robo, have led to the... (More)
In the 25 years, as the first of the syndecan family was cloned, interest in these transmembrane proteoglycans has steadily increased. While four distinct members are present in mammals, one is present in invertebrates, including C. elegans that is such a powerful genetic model. The syndecans, therefore, have a long evolutionary history, indicative of important roles. However, these roles have been elusive. The knockout in the worm has a developmental neuronal phenotype, while knockouts of the syndecans in the mouse are mild and mostly limited to post-natal rather than developmental effects. Moreover, their association with high-affinity receptors, such as integrins, growth factor receptors, frizzled and slit/robo, have led to the notion that syndecans are coreceptors, with minor roles. Given that their heparan sulphate chains can gather many different protein ligands, this gave credence to views that the importance of syndecans lay with their ability to concentrate ligands and that only the extracellular polysaccharide was of significance. Syndecans are increasingly identified with roles in the pathogenesis of many diseases, including tumour progression, vascular disease, arthritis and inflammation. This has provided impetus to understanding syndecan roles in more detail. It emerges that while the cytoplasmic domains of syndecans are small, they have clear interactive capabilities, most notably with the actin cytoskeleton. Moreover, through the binding and activation of signalling molecules, it is likely that syndecans are important receptors in their own right. Here, an overview of syndecan structure and function is provided, with some prospects for the future.
(Less)
- author
- Couchman, John R
; Gopal, Sandeep
LU
; Lim, Hooi Ching
LU
; Nørgaard, Steffen
and Multhaupt, Hinke A B
- publishing date
- 2015-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Genotype, Humans, Inflammation/metabolism, Ligands, Mice, Knockout, Neoplasms/metabolism, Phenotype, Protein Conformation, Receptors, Cell Surface/chemistry, Signal Transduction, Structure-Activity Relationship, Syndecans/chemistry
- in
- International Journal of Experimental Pathology
- volume
- 96
- issue
- 1
- pages
- 1 - 10
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:84923437834
- pmid:25546317
- ISSN
- 0959-9673
- DOI
- 10.1111/iep.12112
- language
- English
- LU publication?
- no
- additional info
- © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.
- id
- 56be3512-fe00-4e51-ad7d-d946653f85fd
- date added to LUP
- 2021-10-25 13:20:30
- date last changed
- 2024-06-16 22:21:39
@article{56be3512-fe00-4e51-ad7d-d946653f85fd,
abstract = {{<p>In the 25 years, as the first of the syndecan family was cloned, interest in these transmembrane proteoglycans has steadily increased. While four distinct members are present in mammals, one is present in invertebrates, including C. elegans that is such a powerful genetic model. The syndecans, therefore, have a long evolutionary history, indicative of important roles. However, these roles have been elusive. The knockout in the worm has a developmental neuronal phenotype, while knockouts of the syndecans in the mouse are mild and mostly limited to post-natal rather than developmental effects. Moreover, their association with high-affinity receptors, such as integrins, growth factor receptors, frizzled and slit/robo, have led to the notion that syndecans are coreceptors, with minor roles. Given that their heparan sulphate chains can gather many different protein ligands, this gave credence to views that the importance of syndecans lay with their ability to concentrate ligands and that only the extracellular polysaccharide was of significance. Syndecans are increasingly identified with roles in the pathogenesis of many diseases, including tumour progression, vascular disease, arthritis and inflammation. This has provided impetus to understanding syndecan roles in more detail. It emerges that while the cytoplasmic domains of syndecans are small, they have clear interactive capabilities, most notably with the actin cytoskeleton. Moreover, through the binding and activation of signalling molecules, it is likely that syndecans are important receptors in their own right. Here, an overview of syndecan structure and function is provided, with some prospects for the future.</p>}},
author = {{Couchman, John R and Gopal, Sandeep and Lim, Hooi Ching and Nørgaard, Steffen and Multhaupt, Hinke A B}},
issn = {{0959-9673}},
keywords = {{Animals; Genotype; Humans; Inflammation/metabolism; Ligands; Mice, Knockout; Neoplasms/metabolism; Phenotype; Protein Conformation; Receptors, Cell Surface/chemistry; Signal Transduction; Structure-Activity Relationship; Syndecans/chemistry}},
language = {{eng}},
number = {{1}},
pages = {{1--10}},
publisher = {{Wiley-Blackwell}},
series = {{International Journal of Experimental Pathology}},
title = {{Fell-Muir Lecture : Syndecans: from peripheral coreceptors to mainstream regulators of cell behaviour}},
url = {{http://dx.doi.org/10.1111/iep.12112}},
doi = {{10.1111/iep.12112}},
volume = {{96}},
year = {{2015}},
}