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

• Published in: iScience 2023-05, Vol.26 (5), p.106773-106773, Article 106773
• Main Authors: Lee, Jisoo, Kim, Soohyun, Lee, Boram, Kim, Yoo-Bin, Kim, Kwang Hwan, Chung, Gehoon, Lee, Sung Joong, Lee, Soojin, Sun, Woong, Park, Hee-Kyung, Choi, Se-Young
• Format: Article
• Language: English
• Subjects: Biological sciences; Molecular biology; Molecular neuroscience; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106773

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 Negr1 knockout (KO) mice was normal. Negr1 KO mice showed tempered carbachol- or thapsigargin-induced intracellular Ca2+ increases and store-operated Ca2+ entry. Of interest, the activity of the large-conductance Ca2+-activated K+ channel (BK channel) was increased, whereas Ca2+-activated Cl− channel ANO1 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 Ca2+ signaling. [Display omitted] •Negr1 knockout mice show reduced salivation•NEGR1 is essential for muscarinic Ca2+ signaling in the submandibular gland•The study provides an explanation for dry mouth among depression patients Biological sciences; Molecular biology; Molecular neuroscience; Neuroscience