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

Jisoo Lee; Soohyun Kim; Boram Lee; Yoo-Bin Kim; Kwang Hwan Kim; Gehoon Chung; Sung Joong Lee; Soojin Lee; Woong Sun; Hee-Kyung Park; Se-Young Choi

doi:10.1016/j.isci.2023.106773

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

iScience. 2023 Apr 26;26(5):106773. doi: 10.1016/j.isci.2023.106773. eCollection 2023 May 19.

Authors

Affiliations

¹ Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea.
² Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine, Seoul 02841, Republic of Korea.
³ Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Republic of Korea.
⁴ Department of Oral Medicine and Oral Diagnosis, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea.

Abstract

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.

Keywords: Biological sciences; Molecular biology; Molecular neuroscience; Neuroscience.