scholarly journals Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity

2005 ◽  
Vol 387 (2) ◽  
pp. 343-353 ◽  
Author(s):  
Jun EGUCHI ◽  
Jun WADA ◽  
Kazuyuki HIDA ◽  
Hong ZHANG ◽  
Takashi MATSUOKA ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Gene Family ◽  
Mrna Expression ◽  
Adhesion Molecule ◽  
Chinese Hamster ◽  
Cell Aggregation ◽  
Cdna Subtraction ◽  
Aggregation Assay ◽  
Oletf Rats ◽  
Type Variable

Few cell adhesion molecules have been reported to be expressed in mature adipocytes, and the significance of cell adhesion process in adipocyte biology is also unknown. In the present study, we identified ACAM (adipocyte adhesion molecule), a novel homologue of the CTX (cortical thymocyte marker in Xenopus) gene family. ACAM cDNA was isolated during PCR-based cDNA subtraction, and its mRNA was shown to be up-regulated in WATs (white adipose tissues) of OLETF (Otsuka Long–Evans Tokushima fatty) rats, an animal model for Type II diabetes and obesity. ACAM, 372 amino acids in total, has a signal peptide, V-type (variable) and C2-type (constant) Ig domains, a single transmembrane segment and a cytoplasmic tail. The amino acid sequence in rat is highly homologous to mouse (94%) and human (87%). ACAM mRNA was predominantly expressed in WATs in OLETF rats, and increased with the development of obesity until 30 weeks of age, which is when the peak of body mass is reached. Western blot analysis revealed that ACAM protein, approx. 45 kDa, was associated with plasma membrane fractions of mature adipocytes isolated from mesenteric and subdermal adipose deposits of OLETF rats. Up-regulation of ACAM mRNAs in obesity was also shown in WATs of genetically obese db/db mice, diet-induced obese ICR mice and human obese subjects. In primary cultured mouse and human adipocytes, ACAM mRNA expression was progressively up-regulated during differentiation. Several stably transfected Chinese-hamster ovary K1 cell lines were established, and the quantification of ACAM mRNA and cell aggregation assay revealed that the degree of homophilic aggregation correlated well with ACAM mRNA expression. In summary, ACAM may be the critical adhesion molecule in adipocyte differentiation and development of obesity.

scholarly journals Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

2000 ◽  
Vol 11 (9) ◽  
pp. 3219-3232 ◽  
Author(s):  
Tetsuro Takeda ◽  
William Y. Go ◽  
Robert A. Orlando ◽  
Marilyn Gist Farquhar
Keyword(s):  
Cell Adhesion ◽  
Cho Cells ◽  
Direct Evidence ◽  
Mdck Cells ◽  
Chinese Hamster ◽  
Cell Aggregation ◽  
Madin Darby Canine Kidney ◽  
Adhesion Properties ◽  
Darby Canine Kidney ◽  
Canine Kidney

Podocalyxin is a major membrane protein of the glomerular epithelium and is thought to be involved in maintenance of the architecture of the foot processes and filtration slits characteristic of this unique epithelium by virtue of its high negative charge. However, until now there has been no direct evidence for podocalyxin's function. Podocalyxin is a type 1 transmembrane sialoprotein with an N-terminal mucin-like domain. To assess its function, we cloned rat podocalyxin and examined the effects of its expression on the cell adhesion properties of stably transfected Chinese hamster ovary (CHO)-K1 and Madin-Darby canine kidney (MDCK) cells and inducible ecdysone receptor–expressing (EcR)-CHO cells. In a cell aggregation assay, CHO-K1 cells expressing high levels of podocalyxin showed complete inhibition of cell aggregation, and MDCK transfectants showed greatly reduced aggregation (∼60–80%) compared with parental cells. In EcR-CHO cells, the expression level of podocalyxin induced by increasing levels of ecdysone analogue correlated closely with the antiadhesion effect. The inhibitory effect of podocalyxin was reversed by treatment of the cells with Arthrobacter ureafacienssialidase, indicating that sialic acid is required for inhibition of cell adhesion. Overexpression of podocalyxin also affected transepithelial resistance and the distribution of junctional proteins in MDCK cells by an unknown mechanism that may involve interaction with the actin cytoskeleton. These results provide direct evidence that podocalyxin functions as an antiadhesin that maintains an open filtration pathway between neighboring foot processes in the glomerular epithelium by charge repulsion.

Role of L1 cell adhesion molecule in gastric carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 56-56
Author(s):  
T. Ito ◽  
Y. Kodera ◽  
C. Tanaka ◽  
N. Ohashi ◽  
G. Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cell Line ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Parental Cell ◽  
Parental Cell Line ◽  
L1 Cell Adhesion Molecule

56 Background: L1 cell adhesion molecule (L1) is a 200-220 kDa transmembrane glycoprotein of the immunoglobulin super family initially identified in neural cells. L1 was detected in ovarian cancer in a stage-dependent manner, was found exclusively in the invasion front of colorectal cancer, and has been considered a stem cell marker in glioma. The authors have shown that mRNA expression of L1 was a significant prognostic factor in gastric cancer (Kodera et al. Gastrointestinal Cancer Symposium 2009, abst 37). Its role in gastric cancer was further investigated. Methods: Expression of L1 was observed by immunostaining in 72 surgically resected pT4A-stage gastric cancer specimens. The association of L1 with peritoneal seeding and prognosis was elucidated. mRNA expression of L1-expressing gastric cancer cell line, KATO3, was suppressed using siRNA (KATO3 L1-). Microarray was used to indentify molecules that differ in expression between KATO3 L1- and the parental cell line. Results: L1 was scarcely stained in non-cancerous epithelial cells and intestinal metaplastic cells. L1 was detected mainly in the cell surface membrane of cancer cells in 15 of 72 specimens, more often in the intestinal type cancer. No correlation was found between L1 expression and detection of cancer cells in the peritoneal washes or development of peritoneal carcinomatosis. Nevertheless, the prognosis of L1-positive cancer was significantly inferior (p = 0.024). Prognosis was particularly poor among 6 cases where L1 was expressed in cancer cells at the invasive front (median survival time 149 days). Of 40,000 genes evaluated in the microarray, mRNA expression of 50 genes were amplified by > 4-fold whereas the expression of 20 genes were attenuated to less than 1/4. Of these, expression of DYRK1A that induces apoptosis in conjunction with p53 was markedly suppressed to less than 1/8. Suppression of DYRK1A in the KATO3 L1- in comparison with the parental cell line was confirmed by RT-PCR. Conclusions: L1 affects prognosis of gastric cancer, particularly when it is expressed in cancer cells at the invasion front. Its role in the biology of gastric cancer has began to be elucidated. No significant financial relationships to disclose.

scholarly journals Identification of putative ligand-binding sites of the integrin α4β1 (VLA-4, CD49d/CD29)

1995 ◽  
Vol 305 (3) ◽  
pp. 945-951 ◽  
Author(s):  
T Kamata ◽  
W Puzon ◽  
Y Takada
Keyword(s):  
Cell Adhesion ◽  
Ligand Binding ◽  
Adhesion Molecule ◽  
Cho Cells ◽  
Binding Sites ◽  
Mammalian Cells ◽  
Cell Adhesion Molecule ◽  
Chinese Hamster ◽  
Ligand Binding Sites ◽  
Cell Adhesion Molecule 1

Integrin alpha 4 beta 1 recognizes both fibronectin (CS-1 sequence) and vascular cell adhesion molecule-1 (VCAM-1). To localize the ligand-binding sites of alpha 4, we located the epitopes for function-blocking anti-alpha 4 monoclonal antibodies (mAbs), including those that recognize previously described (but not yet physically localized) functional epitopes (A, B1, B2 and C) using interspecies alpha 4 chimeras expressed in mammalian cells. Epitopes B1 and B2 were associated with ligand binding, and epitopes A and B2 with homotypic cellular aggregation. mAbs P4C2 (epitope B2), 20E4 and PS/2 were mapped within residues 108-182; mAbs HP2/1 (epitope B1), SG/73 and R1-2 within residues 195-268; mAbs HP1/3 (epitope A) and P4G9 within residues 1-52; and B5G10 (epitope C) within residues 269-548. The data suggest that residues 108-268, which do not include bivalent-cation-binding motifs, are related to VCAM-1 and CS-1 binding, and more N-terminal portions of alpha 4 (residues 1 and 52 and 108-182) to homotypic aggregation. Since mAbs PS/2 and HP2/1 block alpha 4 beta 7 binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the MAdCAM-1-binding site is close to, or overlapping with, VCAM-1- and CS-1-binding sites. The role of Asp-130 of beta 1 in the binding to VCAM-1 and CS-1 peptide was examined. Chinese hamster ovary (CHO) cells expressing beta 1 (D130A) (Asp-130 to Ala mutant of beta 1) and alpha 4 showed much less binding to both ligands than CHO cells expressing wild-type beta 1 and alpha 4 [a dominant negative effects of beta 1 (D130A)], suggesting that Asp-130 of beta 1 is critical for binding to both ligands and that the two ligand share common binding mechanisms [corrected].

scholarly journals Dimerization mechanism and structural features of human LI-cadherin

2020 ◽  
Author(s):  
Anna Yui ◽  
Jose M. M. Caaveiro ◽  
Daisuke Kuroda ◽  
Makoto Nakakido ◽  
Satoru Nagatoishi ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Gastric Cancer ◽  
Cell Adhesion ◽  
Rational Design ◽  
Cell Aggregation ◽  
Structural Features ◽  
Gastric Cancer Cells ◽  
Aggregation Assay ◽  
Colon Cells ◽  
Dependent Cell

AbstractLI-cadherin is a member of cadherin superfamily which is a Ca2+-dependent cell adhesion protein. Its expression is observed on various types of cells in the human body such as normal small intestine and colon cells, and gastric cancer cells. Because its expression is not observed on normal gastric cells, LI-cadherin is a promising target for gastric cancer imaging. However, since the cell adhesion mechanism of LI-cadherin has remained unknown, rational design of therapeutic molecules targeting this cadherin has been complicated. Here, we have studied the homodimerization mechanism of LI-cadherin. We report the crystal structure of the LI-cadherin EC1-4 homodimer. The EC1-4 homodimer exhibited a unique architecture different from that of other cadherins reported so far. The crystal structure also revealed that LI-cadherin possesses a noncanonical calcium ion-free linker between EC2 and EC3. Various biochemical techniques and molecular dynamics (MD) simulations were employed to elucidate the mechanism of homodimerization. We also showed that the formation of the homodimer observed by the crystal structure is necessary for LI-cadherin-dependent cell adhesion by performing cell aggregation assay.

Water maze learning and forebrain mRNA expression of the neural cell adhesion molecule L1

2004 ◽  
Vol 75 (2) ◽  
pp. 172-181 ◽  
Author(s):  
C�sar Venero ◽  
Thomas Tilling ◽  
Irm Hermans-Borgmeyer ◽  
Ana I. Herrero ◽  
Melitta Schachner ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Mrna Expression ◽  
Adhesion Molecule ◽  
Water Maze ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Maze Learning ◽  
Neural Cell ◽  
Neural Cell Adhesion ◽  
Cell Adhesion Molecule L1
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