Cadherin-related protein 24 induces morphological changes and partial cell polarization by facilitating direct cell-cell interactions

Abstract

Cadherin-related protein 24 (CDHR24) is a potential tumor suppressor located apically as well as laterally in polarized cells. Here, the role of CDHR24 in contributing to cell morphology and polarity is examined. CDHR24 was predominantly localized at the nonattached part of nonpolarizing cells while another apically sorted protein, aminopeptidase N, was equally distributed over the plasma membrane. Furthermore, CDHR24 expression induced cell aggregation capacity, indicating direct cell-cell interaction. The transepithelial resistance, however, was elevated in polarized MDCK cells, but not in nonpolarizing CHO cells. Our data propose a model in which CDHR24 is directly involved in cell and tissue morphogenesis.

Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent

“…The functional role of PCDH24 and CDHR5 in nonintestinal tissues and cells is unclear. These proteins have also been found in the liver and kidney [ 31 , 68 ] and have been implicated in contact inhibition of cell proliferation [ 68 , 69 ], morphogenesis [ 31 , 37 , 67 ], colorectal carcinogenesis [ 70 , 71 ], and gallstone disease [ 72 ]. Exploring how different organs in different species express and use PCDH24 and CDHR5 proteins, which have poorly conserved sequences, might provide with a unique opportunity to reveal how evolutionary events structurally encode adhesive and signaling functions in various physiological contexts [ 73 ].…”

“…CDHR5 is most similar to PCDH15, and features cysteine residues predicted to form a disulfide bond at its tip [ 32 , 36 ]. In addition, a mutation in CDHR5, p.R84G (residue numbering throughout the text corresponds to processed proteins, see Methods ), which mimics a deafness-related mutation in PCDH15, interferes with the intermicrovillar links formed by PCDH24 and CDHR5 [ 9 ], suggesting that these proteins interact in a similar fashion to the heterophilic tip-link “handshake” formed by CDH23 and PCDH15 [ 32 , 36 , 37 ].…”

Species-Dependent Heterophilic and Homophilic Cadherin Interactions in Intestinal Intermicrovillar Links

“…The functional role of PCDH24 and CDHR5 in non-intestinal tissues and cells is unclear. These proteins have also been found in the liver and kidney (Goldberg et al, 2000; Okazaki et al, 2002) and have been implicated in contact inhibition of cell proliferation (Okazaki et al, 2002; Ose et al, 2009), morphogenesis (Behrendt et al, 2012; Goldberg et al, 2000; Krahn et al, 2010), colorectal carcinogenesis (Bujko et al, 2015; Losi and Grande, 2014), and gallstone disease (Chuang et al, 2011). Exploring how different organs in different species express and use PCDH24 and CDHR5 proteins, which have poorly conserved sequences, might provide with a unique opportunity to reveal how evolutionary events structurally encode adhesive and signaling functions in various physiological contexts (Dickinson et al, 2011).…”

“…CDHR5 is most similar to PCDH15, and features cysteine residues predicted to form a disulfide bond at its tip (Sotomayor et al, 2014, 2012). In addition, a mutation in CDHR5, R84G (residue numbering throughout the text corresponds to processed proteins, see Methods), which mimics a deafness-related mutation in PCDH15, interferes with the intermicrovillar links formed by PCDH24 and CDHR5 (Crawley et al, 2014b), suggesting that these proteins interact in a similar fashion to the heterophilic tip-link “handshake” formed by CDH23 and PCDH15 (Behrendt et al, 2012; Sotomayor et al, 2014, 2012).…”