title: Sorting Nexin 11 Regulates Lysosomal Degradation of Plasma Membrane TRPV3.
abstract: The trafficking of ion channels to/from the plasma membrane is considered an important mechanism for cellular activity and an interesting approach for disease therapies. The transient receptor potential vanilloid 3 (TRPV3) ion channel is widely expressed in skin keratinocytes, and its trafficking mechanism to/from the plasma membrane is unknown. Here, we report that the vesicular trafficking protein sorting nexin 11 (SNX11) downregulates the level of the TRPV3 plasma membrane protein. Overexpression of SNX11 causes a decrease in the level of TRPV3 current and TRPV3 plasma membrane protein in TRPV3-transfected HEK293T cells. Subcellular localizations and western blots indicate that SNX11 interacts with TRPV3 and targets it to lysosomes for degradation, which is blocked by the lysosomal inhibitors chloroquine and leupeptin. Both TRPV3 and SNX11 are highly expressed in HaCaT cells. We show that TRPV3 agonists-activated Ca(2+) influxes and the level of native TRPV3 total protein in HaCaT cells are decreased by overexpression of SNX11 and increased by knockdown of SNX11. Our findings reveal that SNX11 promotes the trafficking of TRPV3 from the plasma membrane to lysosomes for degradation via protein-protein interactions, which demonstrates a previously unknown function of SNX11 as a regulator of TRPV3 trafficking from the plasma membrane to lysosomes.
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Caiyue
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Ma
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Shikui
authors.initials: S
authors.lastname: Yin
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Shu
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.affiliation: Pharmacological and Physiological Science, School of Medicine, Saint Louis University, St. Louis, MO, USA.
authors.forename: Terrance M
authors.initials: TM
authors.lastname: Egan
authors.affiliation: Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Jufang
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Pan
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
mesh_terms: D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D059748:Proteolysis; D058305:Sorting Nexins / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D058305:Sorting Nexins; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human
keywords: HaCaT cells; TRPV3; degradation; endosomes; lysosomes; sorting nexin 11; trafficking