Evidence for regulated dimerization of cell-cell adhesion molecule (C-CAM) in epithelial cells

Hunter, Irene; Sawa, Hiroki; Edlund, Magnus; Öbrink, Björn

doi:10.1042/bj3200847

Cited by 57 publications

(70 citation statements)

References 53 publications

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“…One possibility is that C-CAM2 regulates the activity of the cytoplasmic domain of C-CAM1. The recent finding that C-CAM can form dimers (Hunter et al 1996) supports such an idea.…”

Section: Discussionsupporting

confidence: 58%

“…It has been suggested that they function as adhesion molecules that organize the sodium channel in specific locations in neurons (Isom and Catterall 1996). Supramolecular complexes of C-CAM have been described in several cell types (Hunter et al 1996). Finally, it has recently been found that C-CAM1 is a negative regulator of cellular growth and that it can suppress tumorigenesis of prostate and colon carcinoma cells (Hsieh et al 1995;Kunath et al 1995).…”

Section: Discussionmentioning

confidence: 99%

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Spatiotemporal Expression of C-CAM in the Rat Placenta

Sawa

Ukita²,

Fukuda³

et al. 1997

J Histochem Cytochem.

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We investigated the expression of the immunoglobulin superfamily cell adhesion molecule, C-CAM, in developing and mature rat placenta. By immunohistochemical staining at the light microscopic level, no C-CAM-expression was seen before Day 9 of gestation, when it appeared in the trophoblasts of ectoplacental cones. On Day 10.5, spongiotrophoblasts and invasive trophoblasts around the maternal vessels of the decidua basalis were stained positively. On Day 12.5, C-CAM was detected in the spongiotrophoblasts of the junctional layer, but labyrinth trophoblasts and secondary giant trophoblasts were not stained. On Day 17.5, C-CAM was found only in the labyrinth and lacunae of the junctional layer. At this stage, both the labyrinth cytotrophoblasts of the maternal blood vessels and the endothelial cells of the embryonic capillaries were strongly stained. Placental tissues from gestational Days 12.5 and 17.5 were analyzed by immunoelectron microscopy to determine the location of C-CAM at the subcellular level. On Day 12.5, positive staining of the spongiotrophoblasts was observed, mainly on surface membranes and microvilli between loosely associated cells. On Day 17.5, staining was found primarily on the microvilli of the maternal luminal surfaces of the labyrinth cytotrophoblasts, and both on the luminal surface and in the cytoplasm of endothelial cells of the embryonic vessels. RT-PCR analysis and Southern blotting of the PCR products revealed expression of mRNA species for both of the major isoforms, C-CAM1 and C-CAM2. Immunoblotting analysis of C-CAM isolated from 12.5-day and 14.5-day placentae showed that it appeared as a broad band with an apparent molecular mass of 110–170 kD. In summary, C-CAM was strongly expressed in a specific spatiotemporal pattern in trophoblasts actively involved in formation of the placental tissue, suggesting an important role in placental development. In the mature placenta, C-CAM expression was confined to the trophoblastic and endothelial cells lining the maternal and embryonic vessels, respectively, suggesting important functions in placental physiology.

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“…One possibility is that C-CAM2 regulates the activity of the cytoplasmic domain of C-CAM1. The recent finding that C-CAM can form dimers (Hunter et al 1996) supports such an idea.…”

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Expression of C-CAM in the Rat Placenta

Sawa

Ukita²,

Fukuda³

et al. 1997

J Histochem Cytochem.

Self Cite

View full text Add to dashboard Cite

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“…It is interesting to observe the seemingly dimeric form of hepaCAM and its mutant in their respective un-cross-linked samples. Although the mechanism resulting in such interaction is unknown to us, Hunter et al (5) and others (12) have observed a similar phenomenon in C-CAM and raise the possibility that C-CAM dimers become covalently linked, perhaps through the action of transglutaminase, an enzyme which catalyzes the formation of ␥-glutamyl-⑀-lysine bonds in a restricted number of cellular proteins. Subcellular localization of hepaCAM in nonpolarized MCF7 cells showed that hepaCAM molecules were recruited to the cytoplasmic membranes at sites of cell-cell attachment.…”

Section: Discussionmentioning

confidence: 99%

Structural and Functional Analyses of a Novel Ig-like Cell Adhesion Molecule, hepaCAM, in the Human Breast Carcinoma MCF7 Cells

Moh

Zhang

Luo

et al. 2005

Journal of Biological Chemistry

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We have recently identified a novel gene, hepaCAM, in liver that encodes a cell adhesion molecule of the immunoglobulin superfamily. In this study, we examined the characteristics of hepaCAM protein and the relationship between its structure and function, in particular its adhesive properties. The wild-type and the cytoplasmic domain-truncated mutants of hepaCAM were transfected into the human breast carcinoma MCF7 cells, and the physiological and biological properties were assessed. Biochemical analyses revealed that hepaCAM is an N-linked glycoprotein phosphorylated in the cytoplasmic domain and that it forms homodimers through cis-interaction on the cell surface. The subcellular localization of hepaCAM appears density-dependent; in well spread cells, hepaCAM is distributed to cell protrusions, whereas in confluent cells, hepaCAM is predominantly accumulated at the sites of cell-cell contacts on the cell membrane. In polarized cells, hepaCAM is recruited to the lateral and basal membranes, and lacking physical interaction, hepaCAM is shown to co-localize with Ecadherin at the lateral membrane. Cell adhesion and motility assays demonstrated that hepaCAM increased cell spreading on the matrices fibronectin and matrigel, delayed cell detachment, and enhanced wound healing. Furthermore, when the cytoplasmic domain was deleted, hepaCAM mutants did not affect cell surface localization and dimer formation. Cell-matrix adhesion, however, was less significantly increased, and cell motility was almost unchanged when compared with the effect of the wild-type hepaCAM. Taken together, the cytoplasmic domain of hepaCAM is essential to its function on cell-matrix interaction and cell motility.

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“…Furthermore, dimerization of selectins has been shown to enhance adhesive tethers (60). Interestingly, dimerization of CEACAM-1 and CEACAM-2 is regulated by calmodulin and calcium ions (68), highlighting the importance of inside-out signaling mechanisms. ICAM-1 exists predominantly as a dimer at the cell surface and binds in this dimeric state with greatly enhanced affinity to the integrin LFA-1 compared with its monomeric form (43).…”

Section: Discussionmentioning

confidence: 99%

The Proprotein Convertase PC5A and a Metalloprotease Are Involved in the Proteolytic Processing of the Neural Adhesion Molecule L1

Kalus

Schnegelsberg

Seidah

et al. 2003

Journal of Biological Chemistry

114

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The transmembrane and multidomain neural adhesion molecule L1 plays important functional roles in the developing and adult nervous system. L1 is proteolytically processed at two distinct sites within the extracellular domain, leading to the generation of different fragments. In this report, we present evidence that the proprotein convertase PC5A is the protease that cleaves L1 in the third fibronectin type III domain, whereas the proprotein convertases furin, PC1, PC2, PACE4, and PC7 are not effective in cleaving L1. Analysis of mutations revealed Arg 845 to be the site of cleavage generating the N-terminal 140-kDa fragment. This fragment was present in the hippocampus, which expresses PC5A, but was not detectable in the cerebellum, which does not express PC5A. The 140-kDa L1 fragment was found to be tightly associated with the full-length 200-kDa L1 molecule. The complex dissociated from the membrane upon cleavage by a protease acting at a more membrane-proximal site of full-length L1. This proteolytic cleavage was inhibited by the metalloprotease inhibitor GM 6001 and enhanced by a calmodulin inhibitor. L1-dependent neurite outgrowth of cerebellar neurons was inhibited by GM 6001, suggesting that proteolytic processing of L1 by a metalloprotease is involved in neurite outgrowth.Proteolytic processing of cell-surface proteins is of prime importance for regulating the functional properties of these proteins (for reviews, see Refs. 1-5). Cleavage of recognition molecules at the cell surface has been implicated in neuronal migration, neurite outgrowth, and synaptic plasticity (6 -13). Among the neural adhesion molecules, L1 has been shown to undergo proteolytic cleavage, which has been suggested to be involved in several functions of this molecule.L1 is a member of the immunoglobulin superfamily consisting of immunoglobulin-like domains and fibronectin type III repeats (for reviews, see Refs. 14 and 15). In the central nervous system, L1 is expressed only by post-mitotic neurons and mainly on non-myelinated axons, whereas in the peripheral nervous system, it is expressed by neurons as well as by non-myelinating Schwann cells. L1 is also expressed by nonneural cells, including normal and transformed cells of hematopoietic and epithelial origin. L1 is involved in neuronal migration, neurite outgrowth, and myelination (for review, see Ref. 14) as well as axon guidance, fasciculation, and regeneration (16,17). Furthermore, it enhances cell survival (18) and synaptic plasticity (19). The importance of L1 in nervous system development is underscored by the abnormal phenotypes of L1 mutations in humans and mice (for review, see Ref. 20). L1 engages in homophilic and heterophilic cell interactions (for reviews, see Refs. 14 and 15) Heterophilic binding partners are the RGD-binding integrins and TAG-1/ axonin-1, F3/F11/contactin, NCAM, CD9, CD24, and phosphacan (Ref. 21 and references therein). These interactions are likely to depend on the presentation of the L1 molecule either as a membrane-bound form or as a proteolytic...

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Evidence for regulated dimerization of cell-cell adhesion molecule (C-CAM) in epithelial cells

Cited by 57 publications

References 53 publications

Spatiotemporal Expression of C-CAM in the Rat Placenta

Spatiotemporal Expression of C-CAM in the Rat Placenta

Structural and Functional Analyses of a Novel Ig-like Cell Adhesion Molecule, hepaCAM, in the Human Breast Carcinoma MCF7 Cells

The Proprotein Convertase PC5A and a Metalloprotease Are Involved in the Proteolytic Processing of the Neural Adhesion Molecule L1

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