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

Abstract

Salivary gland cells, which secrete water in response to neuronal stimulation, are closely connected to other neurons. Transcriptomic studies show that sali-vary glands also express some proteins responsible for neuronal function. How-ever, the physiological functions of these common neuro-exocrine factors in sali-vary glands are largely unknown. Here, we studied the function of Neuronal growth regulator 1 (NEGR1) in the salivary gland cells. NEGR1 was also ex-pressed in mouse and human salivary glands. The structure of salivary glands of Negr1 knockout (KO) mice was normal. Negr1 KO mice showed tempered carbachol-or thapsigargin-induced intracellular Cat' increases and store -oper-ated Cat' entry. Of interest, the activity of the large-conductance Cat' -acti-vated K' channel (BK channel) was increased, whereas Cat'-activated Cl- chan- nelANO1 channel activity was not altered in Negr1 KO mice. Pilocarpine-and carbachol-induced salivation was decreased in Negr1 KO mice. These results suggest that NEGR1 influence salivary secretion though the muscarinic Cat' signaling.