Major depression-related factor NEGR1 controls salivary secretion in mouse submandibular glands.

Salivary gland cells, which secrete water in response to neuronal stimulation, are closely connected to other neurons. Transcriptomic studies show that salivary glands also express some proteins responsible for neuronal function. However, the physiological functions of these common neuro-exocrine factors in salivary glands are largely unknown. Here, we studied the function of Neuronal growth regulator 1 (NEGR1) in the salivary gland cells. NEGR1 was also expressed in mouse and human salivary glands. The structure of salivary glands of knockout (KO) mice was normal. KO mice showed tempered carbachol- or thapsigargin-induced intracellular Ca increases and store-operated Ca entry. Of interest, the activity of the large-conductance Ca-activated K channel (BK channel) was increased, whereas Ca-activated Cl channel ANO1 channel activity was not altered in KO mice. Pilocarpine- and carbachol-induced salivation was decreased in KO mice. These results suggest that NEGR1 influence salivary secretion though the muscarinic Ca signaling.