p130Cas is required for androgen-dependent postnatal development regulation of submandibular glands

Salivary glands develop through epithelial-mesenchymal interactions and are formed through repeated branching. The Crk-associated substrate protein (p130Cas) serves as an adapter that forms a complex with various proteins via integrin and growth factor signaling, with important regulatory roles in several essential cellular processes. We found that p130Cas is expressed in ductal epithelial cells of the submandibular gland (SMG). We generated epithelial tissue-specific p130Cas-deficient ( p130Cas Δepi– ) mice and aimed to investigate the physiological role of p130Cas in the postnatal development of salivary glands. Histological analysis showed immature development of granular convoluted tubules (GCT) of the SMG in male p130Cas Δepi– mice. Furthermore, epidermal growth factor (EGF)-positive secretory granules contained in GCT cells were significantly reduced in p130Cas Δepi– mice with downregulated androgen receptor signaling. Deficiency of p130Cas resulted in a decrease in Rab3D-positive vesicles, disturbed intracellular localization of the cis-Golgi matrix protein GM130, and decreased expression of endoplasmic reticulum (ER) markers such as Lys-Asp-Glu-Leu (KDEL) and calnexin in GCT cells. Thus, p130Cas plays a crucial role in androgen-dependent GCT development in SMG by regulating the formation of the ER-Golgi network.