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(Delta epi-)) 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(Delta epi-) mice. Immunofluorescence staining showed that nuclear-localized androgen receptors (AR) were specifically decreased in GCT cells in p130Cas(Delta epi-) mice. Furthermore, epidermal growth factor-positive secretory granules contained in GCT cells were significantly reduced in p130Cas(Delta epi-) mice with downregulated AR signaling. GCTs lacking p130Cas showed reduced numbers and size of secretory granules, disrupted subcellular localization of the cis-Golgi matrix protein GM130, and sparse endoplasmic reticulum membranes in GCT cells. These results suggest that p130Cas plays a crucial role in androgen-dependent GCT development accompanied with ER-Golgi network formation in SMG by regulating the AR signaling.

Automated summary

Salivary glands develop through epithelial-mesenchymal interactions and are formed through repeated branching. p130Cas protein acts as an adapter, forming complexes with various proteins through integrin and growth factor signaling, regulating essential cellular processes. This study found that p130Cas is expressed in ductal epithelial cells of the submandibular gland (SMG), and its deficiency leads to immature development of granular convoluted tubules (GCT) and downregulated AR signaling.