Nectins, Afadin and Nectin-like Molecules in Mouse Submandibular Glands

The epithelium of the salivary gland exhibits two-tiered organization, which comprises the luminal (acinar and ductal cells) cell layer and the abluminal (myoepithelial and basal cells) cell layer that surrounds the luminal cell layer. These cells adhere to neighboring cells through cell-cell adhesion apparatuses, such as adherens junctions, tight junctions, desmosomes and gap junctions. Cell-cell adhesion molecules at these apparatuses have been identified: cadherins at adherens junctions, claudins and occludin at tight junctions, desmosomal cadherins at desmosomes and connexins at gap junctions. Nectins are immunoglobulin-like cell adhesion molecules which comprise a family with four members (nectin-1, -2, -3, and -4). They are associated with the actin cytoskeleton through the actin filament-binding protein afadin as cadherins are associated with the actin cytoskeleton through the β- and α-catenin complex at adherens junctions. The nectin-afadin complex regulates the formation of adherens junctions cooperatively with the cadherin-catenin complex. In addition to nectins, there are nectin-like molecules (Necls) which resemble nectins in their structures but do not bind afadin. They comprise a family with five members (Necl-1, -2, -3, -4, and -5). Necls interact with nectins and regulate various cellular functions, including cell adhesion, polarization, movement, proliferation, survival, and differentiation, cooperatively with or independently of nectins. In addition to these functions, nectin-1 serves as a receptor for herpes simplex viruses (HSV)-1, nectin-2 serves as a receptor for herpes HSV-2, nectin-4 serves as a receptor for measles virus and Necl-5 serves as a receptor for poliovirus. In this study, we analyzed the expression and localization of nectins, afadin, and E-cadherin in the submandibular gland. The signal for E-cadherin was observed throughout the plasma membrane of the luminal cells in both the ductal and alveolar regions. The signals for nectin-2 and nectin-3 were observed at the apical side of the lateral plasma membrane, presumably adherens junctions, of the luminal cells in the ductal region. The signal for afadin was observed at the apical side of the lateral plasma membrane of the luminal cells in both the ductal and alveolar regions. The signal for Necl-2 was observed at the lateral plasma membrane of the luminal cells in the ductal region. These results suggest that in contrast to E-cadherin, the specific members of nectins and Necls are preferentially expressed in the ductal or acilar region and differentially regulate in the cellular functions of the epithelium of the salivary gland. We are currently analyzing the localization and roles of nectins, Necls and afadin in the submandibular gland.

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