Molecular biology of cadherins in the nervous system

Abstract

Cadherins are cell-cell adhesion molecules belonging to the Ca(2+)-dependent cadherin superfamily. In the last few years the number of cadherins identified in the nervous system has increased considerably. Cadherins are integral membrane glycoproteins. They are structurally closely related and interspecies homologies are high. The function is mediated through a homophilic binding mechanism, and intracellular proteins, directly or indirectly connected to the cadherins and the cytoskeleton, are necessary for cadherin activity. Cadherins have been implicated in segregation and aggregation of tissues at early developmental stages and in growth and guidance of axons during nervous system development. These functions are modified by changes in type(s) and amount of cadherins expressed at different developmental stages. The regulatory elements guiding cadherin expression are currently being elucidated.

Restricted expression of R‐cadherin by brain nuclei and neural circuits of the developing chicken brain

“…Cadherins are a family of molecules that regulate morphogenesis by a Ca"-dependent mechanism in a variety of tissues of the vertebrate embryo (reviewed in Takeichi, 1988;Ranscht, 1991;Takeichi, 1991;Geiger and Ayalon, 1992;Dalseg et al, 1993;Takeichi, 1995). At least ten cadherins are expressed in the vertebrate brain (reviewed in Takeichi et al, 1990;Suzuki et al, 1991;Sano et al, 1993;Redies, 1995).…”

“…Cadherins are morphogenetic molecules regulating the aggregation and sorting of neural cells and the outgrowth and fasciculation of neurites (reviewed in Takeichi et al, 1990;Ranscht, 1991;Dalseg et al, 1993;Redies, 1995). Results from this study suggest that their expression during brain development may be directly involved in the formation of particular brain structures such as brain nuclei, cortical layers, and fiber tracts and, finally, in the establishment of neural circuitry.…”

Molecular Structure of the Apical Junction Complex and Its Contribution to the Paracellular Barrier

“…Cadherin-catenin association is controlled by the carboxy-terminal 72 amino acids; deletion of this C-terminal half of the cytoplasmic domain leads to a loss of the ability to coimmunoprecipitate with any of the catenins. 68 Thus, the catenin-binding sites in the cytoplasmic domain of E-cadherin coincide directly with the sites that are essential for cell-cell and cytoskeletal binding.…”

Comparison of molecular mechanisms mediating cell contact phenomena in model developmental systems: an exploration of universality

“…Binding sequences are thought to be located in the N-terminal EC subdomain EC1 ; the histidine-alanine-valine (HAV) motif, and also amino acids flanking this motif have been implicated. (Takeichi, 1988(Takeichi, , 1990(Takeichi, , 1991(Takeichi, , 1995Kemler, 1992;Tsukita et al, 1992;Grunwald, 1993 ;Gumbiner & McCrea, 1993;Nagafuchi, Tsukita & Takeichi, 1993 ;Nathke, Hinck & Nelson, 1993 ;Pigott & Power, 1993;Sacristan et al, 1993;Behrens, 1994 ;Brar, 1994 ;Dalseg, Gaardsvoll & Bock, 1994 ;Ranscht, 1994;Broders & Thiery, 1995 ;Kirkpatrick & Peifer, 1995 ;Shapiro et al, 1995 a, b ;Gumbiner, 1996;Marrs & Nelson, 1996 ;Steinberg, 1996. ) Classical cadherins interact across the intercellular gap homophilically.…”

“…3 A) has been proposed [based on nuclear magnetic resonance (NMR), and X-ray crystallographic studies of E-cadherin, and N-cadherin] for cadherin-mediated adherens junctions. (Takeichi, 1990(Takeichi, , 1991(Takeichi, , 1995Tsukita et al, 1992 ;Grunwald, 1993 ;Stappert & Kemler, 1993 ;Takeichi et al, 1993 ;Behrens, 1994 ;Dalseg et al, 1994 ;Hulsken, Birchmeier & Behrens, 1994 a, b ;Pavalko & Otey, 1994 ;Overduin et al, 1995;Patel & Gumbiner, 1995 ;Shapiro et al, 1995a, b ;Weis, 1995 ;Gumbiner, 1996;Marrs & Nelson, 1996 ;Nagar et al, 1996. ) It is proposed that the cadherin dimerises laterally at the cell surface.…”