A SNARE Protein Syntaxin 17 Captures CFTR to Potentiate Autophagosomal Clearance Under Stress

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2020 Nov 16

PMID 33191543

Citations 7

Authors

Kavisha Arora

Pramodha Liyanage

Qing Zhong

Anjaparavanda P Naren

Affiliations

Soon will be listed here.

Abstract

Autophagy, a cellular stress response to starvation and bacterial infection, is executed by double-membrane-bound organelles called autophagosomes. Autophagosomes transfer cytosolic material to acidified lysosomes for degradation following soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE)-dependent fusion processes. Many of the autophagy-related disorders stem from defective end-step proteolysis inside lysosomes. The role of epithelial cystic fibrosis (CF) transmembrane conductance regulator (CFTR) chloride channel has been argued to be critical for efficient lysosomal clearance; however, its context to autophagic clearance and the underlying mechanism is poorly defined. Here, we report that syntaxin17 (Stx17), an autophagic SNARE protein interacts with CFTR under nutritional stress and bacterial infection and incorporates it into mature autophagosomes to mediate an efficient lysosomal clearance. Lack of CFTR function and Stx17 and loss of CFTR-Stx17 interaction impairs bacterial clearance. We discover a specialized role of the Stx17-CFTR protein complex that is critical to prevent defective autophagy as has been the reported scenario in CF airway epithelial cells, infectious diseases, and lysosomal clearance disorders.

Citing Articles

Functional Consequences of CFTR Interactions in Cystic Fibrosis.

Ramananda Y, Naren A, Arora K Int J Mol Sci. 2024; 25(6).

PMID: 38542363 PMC: 10970640. DOI: 10.3390/ijms25063384.

Recent progresses in the late stages of autophagy.

Zhu Y, Liu F, Jian F, Rong Y Cell Insight. 2024; 3(2):100152.

PMID: 38435435 PMC: 10904915. DOI: 10.1016/j.cellin.2024.100152.

Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.

Chevalier B, Baatallah N, Najm M, Castanier S, Jung V, Pranke I Int J Mol Sci. 2022; 23(16).

PMID: 36012204 PMC: 9408702. DOI: 10.3390/ijms23168937.

Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.

Jaganathan D, Bruscia E, Kopp B Int J Mol Sci. 2022; 23(14).

PMID: 35887098 PMC: 9319215. DOI: 10.3390/ijms23147750.

Proximity Profiling of the CFTR Interaction Landscape in Response to Orkambi.

Iazzi M, Astori A, St-Germain J, Raught B, Gupta G Int J Mol Sci. 2022; 23(5).

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References

Li C, Dandridge K, Di A, Marrs K, Harris E, Roy K . Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions. J Exp Med. 2005; 202(7):975-86. PMC: 2213164. DOI: 10.1084/jem.20050421. View

Barasch J, Kiss B, Prince A, Saiman L, Gruenert D, Al-Awqati Q . Defective acidification of intracellular organelles in cystic fibrosis. Nature. 1991; 352(6330):70-3. DOI: 10.1038/352070a0. View

Ravikumar B, Moreau K, Jahreiss L, Puri C, Rubinsztein D . Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat Cell Biol. 2010; 12(8):747-57. PMC: 2923063. DOI: 10.1038/ncb2078. View

Ma J, Zhao J, Drumm M, Xie J, DAVIS P . Function of the R domain in the cystic fibrosis transmembrane conductance regulator chloride channel. J Biol Chem. 1997; 272(44):28133-41. DOI: 10.1074/jbc.272.44.28133. View

Huang F, Rock J, Harfe B, Cheng T, Huang X, Jan Y . Studies on expression and function of the TMEM16A calcium-activated chloride channel. Proc Natl Acad Sci U S A. 2009; 106(50):21413-8. PMC: 2781737. DOI: 10.1073/pnas.0911935106. View

Shrestha C, Assani K, Rinehardt H, Albastroiu F, Zhang S, Shell R . Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages. PLoS One. 2017; 12(10):e0186169. PMC: 5642023. DOI: 10.1371/journal.pone.0186169. View

Tosco A, De Gregorio F, Esposito S, De Stefano D, Sana I, Ferrari E . A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR. Cell Death Differ. 2016; 23(8):1380-93. PMC: 4947669. DOI: 10.1038/cdd.2016.22. View

Davies J . Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatr Respir Rev. 2002; 3(2):128-34. DOI: 10.1016/s1526-0550(02)00003-3. View

Travassos L, Carneiro L, Ramjeet M, Hussey S, Kim Y, Magalhaes J . Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol. 2009; 11(1):55-62. DOI: 10.1038/ni.1823. View

10.

Bonfield T . Macrophage Dysfunction in Cystic Fibrosis: A Therapeutic Target to Enhance Self-Immunity. Am J Respir Crit Care Med. 2015; 192(12):1406-7. DOI: 10.1164/rccm.201509-1811ED. View

11.

Yuan K, Huang C, Fox J, Laturnus D, Carlson E, Zhang B . Autophagy plays an essential role in the clearance of Pseudomonas aeruginosa by alveolar macrophages. J Cell Sci. 2012; 125(Pt 2):507-15. PMC: 3283879. DOI: 10.1242/jcs.094573. View

12.

Penmatsa H, Zhang W, Yarlagadda S, Li C, Conoley V, Yue J . Compartmentalized cyclic adenosine 3',5'-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains. Mol Biol Cell. 2010; 21(6):1097-110. PMC: 2836961. DOI: 10.1091/mbc.e09-08-0655. View

13.

Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T . Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell. 2006; 10(6):839-50. DOI: 10.1016/j.devcel.2006.04.002. View

14.

Cadwell K, Liu J, Brown S, Miyoshi H, Loh J, Lennerz J . A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008; 456(7219):259-63. PMC: 2695978. DOI: 10.1038/nature07416. View

15.

Wolfe D, Lee J, Kumar A, Lee S, Orenstein S, Nixon R . Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification. Eur J Neurosci. 2013; 37(12):1949-61. PMC: 3694736. DOI: 10.1111/ejn.12169. View

16.

Schroeder T, Reiniger N, Meluleni G, Grout M, Coleman F, Pier G . Transgenic cystic fibrosis mice exhibit reduced early clearance of Pseudomonas aeruginosa from the respiratory tract. J Immunol. 2001; 166(12):7410-8. DOI: 10.4049/jimmunol.166.12.7410. View

17.

Russell R, Yuan H, Guan K . Autophagy regulation by nutrient signaling. Cell Res. 2013; 24(1):42-57. PMC: 3879708. DOI: 10.1038/cr.2013.166. View

18.

Lieberman A, Puertollano R, Raben N, Slaugenhaupt S, Walkley S, Ballabio A . Autophagy in lysosomal storage disorders. Autophagy. 2012; 8(5):719-30. PMC: 3378416. DOI: 10.4161/auto.19469. View

19.

Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y . ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature. 2015; 520(7548):563-6. PMC: 4442024. DOI: 10.1038/nature14147. View

20.

Junkins R, Shen A, Rosen K, McCormick C, Lin T . Autophagy enhances bacterial clearance during P. aeruginosa lung infection. PLoS One. 2013; 8(8):e72263. PMC: 3756076. DOI: 10.1371/journal.pone.0072263. View