Cholangiocytes express an isoform of soluble adenylyl cyclase that is N‐linked glycosylated and secreted in extracellular vesicles

Author:

Go Simei12ORCID,Li Hang Lam12,Chang Jung‐Chin12,Verhoeven Arthur J.12,Elferink Ronald P. J. Oude12

Affiliation:

1. Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam Amsterdam the Netherlands

2. Amsterdam Gastroenterology and Metabolism (AG&M) Research Institute, Amsterdam UMC, University of Amsterdam Amsterdam the Netherlands

Abstract

AbstractSoluble adenylyl cyclase (sAC)‐derived cAMP regulates various cellular processes; however, the regulatory landscape mediating sAC protein levels remains underexplored. We consistently observed a 85 kD (sAC85) or 75 kD (sAC75) sAC protein band under glucose‐sufficient or glucose‐deprived states, respectively, in H69 cholangiocytes by immunoblotting. Deglycosylation by PNGase‐F demonstrated that both sAC75 and sAC85 are N‐linked glycosylated proteins with the same polypeptide backbone. Deglycosylation with Endo‐H further revealed that sAC75 and sAC85 carry distinct sugar chains. We observed release of N‐linked glycosylated sAC (sACEV) in extracellular vesicles under conditions that support intracellular sAC85 (glucose‐sufficient) as opposed to sAC75 (glucose‐deprived) conditions. Consistently, disrupting the vesicular machinery affects the maturation of intracellular sAC and inhibits the release of sACEV into extracellular vesicles. The intracellular turnover of sAC85 is extremely short (t1/2 ~30 min) and release of sACEV in the medium was detected within 3 h. Our observations support the maturation and trafficking in cholangiocytes of an N‐linked glycosylated sAC isoform that is rapidly released into extracellular vesicles.

Funder

Academisch Medisch Centrum

Publisher

Wiley

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Soluble adenylyl cyclase, the cell-autonomous member of the family;Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease;2024-02

2. Opposite regulation of glycogen metabolism by cAMP produced in the cytosol and at the plasma membrane;Biochimica et Biophysica Acta (BBA) - Molecular Cell Research;2024-01

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