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Gene Review

PCDH1  -  protocadherin 1

Homo sapiens

Synonyms: Cadherin-like protein 1, PC42, PCDH42, Protocadherin-1, Protocadherin-42, ...
 
 
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Disease relevance of PCDH1

 

High impact information on PCDH1

  • A striking organization of a large family of human neural cadherin-like cell adhesion genes [6].
  • This unusual organization has interesting implications regarding the molecular code required to establish complex networks of neuronal connections in the brain and the mechanisms of cell-specific cadherin-like gene expression [6].
  • Deletion mapping showed that intact extracellular cadherin-like repeats of Dsc1a (Arg1-Thr170) are required for the translocation of Dsg2 [7].
  • The Pcdh-alpha gene cluster encodes a family of 14 distinct cadherin-like cell surface proteins that are expressed in neurons and are present at synaptic junctions [8].
  • In individual neurons, only one (and rarely two) of the Pcdh alpha1-12 promoters is independently and randomly activated on each chromosome [8].
 

Chemical compound and disease context of PCDH1

 

Biological context of PCDH1

  • Cell aggregation assays in the presence or absence of metalloprotease inhibitors strongly suggest that the ectodomain shedding events modulate the cell adhesion role of Pcdh gamma [10].
  • A large family of neural protocadherin (Pcdh) proteins is encoded by three closely linked mammalian gene clusters (alpha, beta, and gamma) [11].
  • The clustered Pcdh family has multiple variable exons that differ somewhat in number and sequence across vertebrate species [12].
  • Desmosomal glycoproteins II and III. Cadherin-like junctional molecules generated by alternative splicing [13].
  • The amino acid sequences of 82 different cadherin-like repeats from 13 known members of the cadherin superfamily were compared for six highly conserved regions, and a frequency matrix represented as amino acids versus position matrix was calculated based on the alignment [14].
 

Anatomical context of PCDH1

 

Associations of PCDH1 with chemical compounds

  • In contrast to N-cadherin shedding, which was activated by N-methyl-D-aspartic acid receptor activation in neuronal cells, Pcdh gamma shedding was induced by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate stimulation, suggesting differential regulation mechanisms of cadherin-mediated functions at synapses [10].
  • Molecular modeling of the extracellular domain of the RET receptor tyrosine kinase reveals multiple cadherin-like domains and a calcium-binding site [20].
  • RESULTS: PCDH-PC expression induced Wnt signaling in CaP cells and permitted androgen-independent growth of hormone-sensitive CaP cells [4].
  • Sequence analysis indicated that the deduced protein sequence was most similar to the cadherin-like from Heliothis virescens with 84.2% identity and highly similar to three other lepidopteran cadherin from Bombyx mori, Manduca sexta and Pectinophora gossypiella, with the sequence identities of 60.3.6%, 57.5% and 51.0%, respectively [21].
  • Preliminary data indicated an up-regulation at early time points (15-30 min) of a number of genes involved in transportation (e.g. the sodium and chloride dependent taurine transporter) and receptors (e.g. ZAP70 and protocadherin 42 precursor) [22].
 

Regulatory relationships of PCDH1

  • The identification of ADAM10 as the protease responsible for constitutive and regulated Pcdh gamma shedding may therefore provide new insight into the regulation of Pcdh gamma functions [10].
 

Other interactions of PCDH1

 

Analytical, diagnostic and therapeutic context of PCDH1

  • The models of the cadherin-like domains of human RET represent valuable tools with which to guide future site-directed mutagenesis studies aimed at identifying residues involved in ligand binding and receptor activation [20].
  • Cloning, sequence analysis and expression pattern of mouse desmocollin 2 (DSC2), a cadherin-like adhesion molecule [28].
  • PCDH-PC mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ hybridization [4].
  • Immunohistochemistry showed the cadherin-like proteins are present in the insect midgut apical membrane, which is the target site of Cry toxins [9].
  • The full-length cDNA encoding cadherin-like of Helicoverpa armigera is cloned by degenerate PCR and RACE techniques and the gene was designated as BtR-harm, which is 5581 bp in full-length, encoding 1730 amino acid residues (BtR-harm was deposited in GenBank and the accession number is AF519180) [21].

References

  1. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Bork, J.M., Peters, L.M., Riazuddin, S., Bernstein, S.L., Ahmed, Z.M., Ness, S.L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C.R., Wayne, S., Bellman, S., Desmukh, D., Ahmed, Z., Khan, S.N., Kaloustian, V.M., Li, X.C., Lalwani, A., Riazuddin, S., Bitner-Glindzicz, M., Nance, W.E., Liu, X.Z., Wistow, G., Smith, R.J., Griffith, A.J., Wilcox, E.R., Friedman, T.B., Morell, R.J. Am. J. Hum. Genet. (2001) [Pubmed]
  2. Cloning of the gene for human pemphigus vulgaris antigen (desmoglein 3), a desmosomal cadherin. Characterization of the promoter region and identification of a keratinocyte-specific cis-element. Silos, S.A., Tamai, K., Li, K., Kivirikko, S., Kouba, D., Christiano, A.M., Uitto, J. J. Biol. Chem. (1996) [Pubmed]
  3. Cytotoxic activity of Bacillus thuringiensis Cry proteins on mammalian cells transfected with cadherin-like Cry receptor gene of Bombyx mori (silkworm). Tsuda, Y., Nakatani, F., Hashimoto, K., Ikawa, S., Matsuura, C., Fukada, T., Sugimoto, K., Himeno, M. Biochem. J. (2003) [Pubmed]
  4. Protocadherin-PC promotes androgen-independent prostate cancer cell growth. Terry, S., Queires, L., Gil-Diez-de-Medina, S., Chen, M.W., de la Taille, A., Allory, Y., Tran, P.L., Abbou, C.C., Buttyan, R., Vacherot, F. Prostate (2006) [Pubmed]
  5. DC-CLM, a cadherin-like molecule cloned from human dendritic cells, inhibits growth of breast cancer cells. Jiang, Y., Wan, T., Chen, G., Xiu, F., Xia, D., Zhang, W., Zhou, X., Cao, X. J. Cancer Res. Clin. Oncol. (2003) [Pubmed]
  6. A striking organization of a large family of human neural cadherin-like cell adhesion genes. Wu, Q., Maniatis, T. Cell (1999) [Pubmed]
  7. Direct Ca2+-dependent heterophilic interaction between desmosomal cadherins, desmoglein and desmocollin, contributes to cell-cell adhesion. Chitaev, N.A., Troyanovsky, S.M. J. Cell Biol. (1997) [Pubmed]
  8. Identification of long-range regulatory elements in the protocadherin-{alpha} gene cluster. Ribich, S., Tasic, B., Maniatis, T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Expression of Cry1Ac cadherin receptors in insect midgut and cell lines. Aimanova, K.G., Zhuang, M., Gill, S.S. J. Invertebr. Pathol. (2006) [Pubmed]
  10. Regulated ADAM10-dependent ectodomain shedding of gamma-protocadherin C3 modulates cell-cell adhesion. Reiss, K., Maretzky, T., Haas, I.G., Schulte, M., Ludwig, A., Frank, M., Saftig, P. J. Biol. Chem. (2006) [Pubmed]
  11. Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation. Zhang, T., Haws, P., Wu, Q. Genome Res. (2004) [Pubmed]
  12. The role and expression of the protocadherin-alpha clusters in the CNS. Hirayama, T., Yagi, T. Curr. Opin. Neurobiol. (2006) [Pubmed]
  13. Desmosomal glycoproteins II and III. Cadherin-like junctional molecules generated by alternative splicing. Parker, A.E., Wheeler, G.N., Arnemann, J., Pidsley, S.C., Ataliotis, P., Thomas, C.L., Rees, D.A., Magee, A.I., Buxton, R.S. J. Biol. Chem. (1991) [Pubmed]
  14. Motifs of cadherin- and fibronectin type III-related sequences and evolution of the receptor-type-protein tyrosine kinases: sequence similarity between proto-oncogene ret and cadherin family. Kuma, K., Iwabe, N., Miyata, T. Mol. Biol. Evol. (1993) [Pubmed]
  15. Expression and function of glial cell line-derived neurotrophic factor family ligands and their receptors on human immune cells. Vargas-Leal, V., Bruno, R., Derfuss, T., Krumbholz, M., Hohlfeld, R., Meinl, E. J. Immunol. (2005) [Pubmed]
  16. Structural analysis and expression of human desmoglein: a cadherin-like component of the desmosome. Nilles, L.A., Parry, D.A., Powers, E.E., Angst, B.D., Wagner, R.M., Green, K.J. J. Cell. Sci. (1991) [Pubmed]
  17. PCNS: a novel protocadherin required for cranial neural crest migration and somite morphogenesis in Xenopus. Rangarajan, J., Luo, T., Sargent, T.D. Dev. Biol. (2006) [Pubmed]
  18. Common genomic structure for the Lepidoptera cadherin-like genes. Bel, Y., Escriche, B. Gene (2006) [Pubmed]
  19. Visualisation by electron microscopy of the unique part of the cytoplasmic domain of a desmoglein, a cadherin-like protein of the desmosome type of cell junction. Rutman, A.J., Buxton, R.S., Burdett, I.D. FEBS Lett. (1994) [Pubmed]
  20. Molecular modeling of the extracellular domain of the RET receptor tyrosine kinase reveals multiple cadherin-like domains and a calcium-binding site. Anders, J., Kjar, S., Ibáñez, C.F. J. Biol. Chem. (2001) [Pubmed]
  21. Gene cloning and expression of cadherin in midgut of Helicoverpa armigera and its Cry1A binding region. Wang, G., Wu, K., Liang, G., Guo, Y. Sci. China, C, Life Sci. (2005) [Pubmed]
  22. Gene expression analysis of EpiDerm following exposure to SLS using cDNA microarrays. Fletcher, S.T., Baker, V.A., Fentem, J.H., Basketter, D.A., Kelsell, D.P. Toxicology in vitro : an international journal published in association with BIBRA. (2001) [Pubmed]
  23. CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness. Astuto, L.M., Bork, J.M., Weston, M.D., Askew, J.W., Fields, R.R., Orten, D.J., Ohliger, S.J., Riazuddin, S., Morell, R.J., Khan, S., Riazuddin, S., Kremer, H., van Hauwe, P., Moller, C.G., Cremers, C.W., Ayuso, C., Heckenlively, J.R., Rohrschneider, K., Spandau, U., Greenberg, J., Ramesar, R., Reardon, W., Bitoun, P., Millan, J., Legge, R., Friedman, T.B., Kimberling, W.J. Am. J. Hum. Genet. (2002) [Pubmed]
  24. Plakoglobin binding by human Dsg3 (pemphigus vulgaris antigen) in keratinocytes requires the cadherin-like intracytoplasmic segment. Roh, J.Y., Stanley, J.R. J. Invest. Dermatol. (1995) [Pubmed]
  25. Chlamydia trachomatis disrupts N-cadherin-dependent cell-cell junctions and sequesters beta-catenin in human cervical epithelial cells. Prozialeck, W.C., Fay, M.J., Lamar, P.C., Pearson, C.A., Sigar, I., Ramsey, K.H. Infect. Immun. (2002) [Pubmed]
  26. Identification and expression analysis of the human mu-protocadherin gene in fetal and adult kidneys. Goldberg, M., Wei, M., Tycko, B., Falikovich, I., Warburton, D. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  27. Culture of melanoma cells in 3-dimensional architectures results in impaired immunorecognition by cytotoxic T lymphocytes specific for Melan-A/MART-1 tumor-associated antigen. Ghosh, S., Rosenthal, R., Zajac, P., Weber, W.P., Oertli, D., Heberer, M., Martin, I., Spagnoli, G.C., Reschner, A. Ann. Surg. (2005) [Pubmed]
  28. Cloning, sequence analysis and expression pattern of mouse desmocollin 2 (DSC2), a cadherin-like adhesion molecule. Lorimer, J.E., Hall, L.S., Clarke, J.P., Collins, J.E., Fleming, T.P., Garrod, D.R. Mol. Membr. Biol. (1994) [Pubmed]
 
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