Regulated clustering of variant CD44 proteins increases their hyaluronate binding capacity.

Sleeman, Jonathan; Rudy, Wolfgang; Hofmann, Martin; Moll, Jürgen; Herrlich, Peter; Ponta, Helmut

doi:10.1083/jcb.135.4.1139

Cited by 134 publications

(120 citation statements)

References 36 publications

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“…Dimerization is a well-known mechanism for activation of receptor kinases [62]. Intramembrane clustering has also been shown to be important for activation of downstream activities of non-catalytic receptors [63,64] and cell-adhesion molecules [65][66][67][68].…”

Section: Core-protein-mediated Oligomerizationmentioning

confidence: 99%

Syndecans: multifunctional cell-surface co-receptors

Carey

1997

Biochemical Journal

620

497

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This review will summarize our current state of knowledge of the structure, biochemical properties and functions of syndecans, a family of transmembrane heparan sulphate proteoglycans. Syndecans bind a variety of extracellular ligands via their covalently attached heparan sulphate chains. Syndecans have been proposed to play a role in a variety of cellular functions, including cell proliferation and cell–matrix and cell–cell adhesion. Syndecan expression is highly regulated and is cell-type- and developmental-stage-specific. The main function of syndecans appears to be to modulate the ligand-dependent activation of primary signalling receptors at the cell surface. Principal functions of the syndecan core proteins are to target the heparan sulphate chains to the appropriate plasma-membrane compartment and to interact with components of the actin-based cytoskeleton. Several functions of the syndecans, including syndecan oligomerization and actin cytoskeleton association, have been localized to specific structural domains of syndecan core proteins.

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Section: Core-protein-mediated Oligomerizationmentioning

confidence: 99%

Syndecans: multifunctional cell-surface co-receptors

Carey

1997

Biochemical Journal

620

497

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“…However, co-immunoprecipitation studies did not provide evidence for CD49d preferentially associating with CD44v. Whether the HA binding that was observed in AA LNC might be linked to the expression of CD44v [47] could not be evaluated because available CD44v-specific antibodies do not interfere with HA binding (unpublished finding).…”

Section: General Commentsmentioning

confidence: 99%

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

2006

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CD44 is involved in leukocyte migration and activation and has recently been reported to contribute to leukocyte extravasation by associating with CD49d. We explored whether similar changes in CD44 activity are seen in vivo using murine alopecia areata (AA) as a chronic, organ‐related autoimmune disease model system. Expression of the activated, hyaluronan‐binding form of CD44, and of CD49d, was elevated in draining lymph node cells (LNC) of AA‐affected mice as compared to control mice. LNC of AA mice displayed increased motility, proliferative activity and apoptosis resistance, which were equally well inhibited by anti‐CD44 and anti‐CD49d. The latter is the sequelae of the association between CD44 and CD49d that is seen in activated lymphocytes. Significantly, due to CD44‐CD49d complex formation, CD44 gains access to focal adhesion kinase and CD49d gains access to CD44‐associated lck and ezrin, such that downstream kinases become activated via CD44 or CD49d engagement. Thus, by their association, CD44 and CD49d mutually avail themselves of the partner's signaling pathways and the ligand binding of each one triggers signaling pathways of both. This strongly influences the lymphocytes’ activation state and function.

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“…In tumor cells, a correlation between increased ectopic expression of CD44v5-7 on the cell surface and increased soluble HA binding capacity was observed (28). Those authors postulated that the regulation of CD44 clustering, mediated by factors such as the presence of variant exons and glycosylation, allows cells to regulate their HA binding capacities.…”

Section: Discussionmentioning

confidence: 99%

Increase in the expression of the transmembrane surface receptor CD44v6 on chondrocytes in animals with osteoarthritis

Tibesku¹,

Szuwart²,

Ocken³

et al. 2005

Arthritis & Rheumatism

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Objective. To evaluate the expression of CD44v6 on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA).Methods. In 12 NZW rabbits, the anterior cruciate ligament (ACL) was resected to create anterior instability of the knee. In 12 control rabbits, only a sham operation, without resection of the ACL, was performed. Four animals from each group were killed at 3, 6, and 12 weeks. After opening the knee joint, OA was macroscopically graded and hyaline cartilage of the load-bearing area was evaluated histologically according to the Mankin scale and by immunostaining for CD44v6.Results. There was a positive linear correlation between the time after surgery and the macroscopic and histologic OA scores. The scores in the control group were constant over the time course. Immunostaining showed constant expression of CD44v6 in the control group. In the experimental group, a positive linear correlation between CD44v6 expression and macroscopic and histologic grades was found.Conclusion. The results show an in vivo increase in the expression of the hyaluronan receptor CD44 over the time course of OA. Further studies are needed to evaluate whether this pattern applies to humans and whether new treatment approaches could evolve from this knowledge.

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Regulated clustering of variant CD44 proteins increases their hyaluronate binding capacity.

Cited by 134 publications

References 36 publications

Syndecans: multifunctional cell-surface co-receptors

Syndecans: multifunctional cell-surface co-receptors

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

Increase in the expression of the transmembrane surface receptor CD44v6 on chondrocytes in animals with osteoarthritis

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