Role of ClC-7 in Biogenesis of Lamellar Body in Alveolar Type Ⅱ Cells

doi:10.3870/j.issn.1672-8009.2025.06.001

Journal of Medical Molecular Biology ›› 2025, Vol. 22 ›› Issue (6): 531-538.doi: 10.3870/j.issn.1672-8009.2025.06.001

• Original Articles • Next Articles

Role of ClC-7 in Biogenesis of Lamellar Body in Alveolar Type Ⅱ Cells

ZHOU Zixuan, HAO Zhenhua, LI Wei

Beijing Children’s Hospital of Capital Medical University,Genetics and Birth Defects Control Center,National Center for Children’s Health,Beijing Key Laboratory for Genetics of Birth Defects of Beijing Pediatric Research Institute,MOE Key Laboratory of Major Diseases in Children,Beijing,100045,China

Received:2025-02-10 Online:2025-11-30 Published:2025-12-25
Contact: LI Wei(E-mail:liwei@bch.com.cn),HAO Zhenhua(E-mail:nanshayu@163.com)
Supported by:
National Natural Science Foundation of China(No.32293204,No.32271157)

Abstract

Abstract: Objective To explore the role of ClC-7 in lamellar body(LB)biogenesis and to investigate the possible pathogenesis of some ClC-7 mutants from patients. Methods siRNA knockdown was employed to decrease the expression of ClC-7 in A549 cells,followed by observing LB morphological changes using laser confocal microscopy and transmission electron microscopy.Wild-type and mutant ClC-7 plasmids were constructed,and the co-localization of ClC-7 with LB and other organelles was observed using immunofluorescence method. Results ClC-7 was localized to LBs and lysosomes.The size of LBs in the ClC-7 knockdown cells was enlarged.Mutations of p.G203D,p.G215R,p.G292E,p.R403Q,and p.L766P,led to mislocalization of ClC-7 to the endoplasmic reticulum.Mutation of p.P470L lead to partial retention of ClC-7 on early endosomes but mostly localizes on LBs. Conclusion ClC-7 in A549 cells is localized to both LBs and lysosomes.Knockdown of ClC-7 in cultured cells leads to enlarged LBs.Most of the mutated ClC-7 cannot be correctly localized on lamellar bodies and lysosomes.

Key words: ClC-7, lamellar body, lysosome-related organelles, alveolar type Ⅱ cell, interstitial lung disease

CLC Number:

R394.3

ZHOU Zixuan, HAO Zhenhua, LI Wei. Role of ClC-7 in Biogenesis of Lamellar Body in Alveolar Type Ⅱ Cells[J]. Journal of Medical Molecular Biology, 2025, 22(6): 531-538.

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Role of ClC-7 in Biogenesis of Lamellar Body in Alveolar Type Ⅱ Cells

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