Faculty Opinions recommendation of PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel.

2019 ◽  
Author(s):  
Rajini Rao
Keyword(s):  
Membrane Protein ◽  
Chloride Channel ◽  
Evolutionarily Conserved

scholarly journals PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. 395-399 ◽  
Author(s):  
Junhua Yang ◽  
Jianan Chen ◽  
Maria del Carmen Vitery ◽  
James Osei-Owusu ◽  
Jiachen Chu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Rna Interference ◽  
Membrane Protein ◽  
Chloride Channel ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Acidic Ph ◽  
Evolutionarily Conserved ◽  
Cancer And Inflammation ◽  
Broad Role

Severe local acidosis causes tissue damage and pain, and is one of the hallmarks of many diseases including ischemia, cancer, and inflammation. However, the molecular mechanisms of the cellular response to acid are not fully understood. We performed an unbiased RNA interference screen and identified PAC (TMEM206) as being essential for the widely observed proton-activated Cl− (PAC) currents (ICl,H). Overexpression of human PAC in PAC knockout cells generated ICl,H with the same characteristics as the endogenous ones. Zebrafish PAC encodes a PAC channel with distinct properties. Knockout of mouse Pac abolished ICl,H in neurons and attenuated brain damage after ischemic stroke. The wide expression of PAC suggests a broad role for this conserved Cl− channel family in physiological and pathological processes associated with acidic pH.

scholarly journals Immunoisolaton of the Yeast Golgi Subcompartments and Characterization of a Novel Membrane Protein, Svp26, Discovered in the Sed5-Containing Compartments

2005 ◽  
Vol 25 (17) ◽  
pp. 7696-7710 ◽  
Author(s):  
Hironori Inadome ◽  
Yoichi Noda ◽  
Hiroyuki Adachi ◽  
Koji Yoda
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Golgi Apparatus ◽  
Membrane Protein ◽  
Considerable Portion ◽  
Marker Proteins ◽  
Evolutionarily Conserved ◽  
Golgi Compartment

ABSTRACT The Golgi apparatus consists of a set of vesicular compartments which are distinguished by their marker proteins. These compartments are physically separated in the Saccharomyces cerevisiae cell. To characterize them extensively, we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins. The composition of proteins was mostly consistent with the position of each compartment in the traffic. We found six uncharacterized but evolutionarily conserved proteins and named them Svp26 (Sed5 compartment vesicle protein of 26 kDa), Tvp38, Tvp23, Tvp18, Tvp15 (Tlg2 compartment vesicle proteins of 38, 23, 18, and 15 kDa), and Gvp36 (Golgi vesicle protein of 36 kDa). The localization of Svp26 in the early Golgi compartment was confirmed by microscopic and biochemical means. Immunoprecipitation indicated that Svp26 binds to itself and a Golgi mannosyltransferase, Ktr3. In the absence of Svp26, a considerable portion of Ktr3 was mislocalized in the endoplasmic reticulum. Our data suggest that Svp26 has a novel role in retention of a subset of membrane proteins in the early Golgi compartments.

scholarly journals Isolation and Expression Profile of the Ca2+-Activated Chloride Channel-like Membrane Protein 6 Gene inXenopus laevis

2011 ◽  
Vol 27 (2) ◽  
pp. 109 ◽  
Author(s):  
Ra Mi Lee ◽  
Rae Hyung Ryu ◽  
Seong Won Jeong ◽  
Soo Jin Oh ◽  
Hue Huang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Expression Profile ◽  
Chloride Channel ◽  
Inxenopus Laevis

scholarly journals Jagunal is required for reorganizing the endoplasmic reticulum during Drosophila oogenesis

2007 ◽  
Vol 176 (7) ◽  
pp. 941-952 ◽  
Author(s):  
Sangil Lee ◽  
Lynn Cooley
Keyword(s):  
Endoplasmic Reticulum ◽  
Drosophila Melanogaster ◽  
Membrane Protein ◽  
Membrane Traffic ◽  
Protein Loss ◽  
Drosophila Oogenesis ◽  
Vesicular Traffic ◽  
Lateral Membrane ◽  
Evolutionarily Conserved ◽  
Er Membrane

Vesicular traffic in the Drosophila melanogaster oocyte occurs actively during vitellogenesis. Although endocytosis in the oocyte has been well characterized, exocytic vesicular traffic is less well understood. We show that the oocyte endoplasmic reticulum (ER) becomes concentrated into subcortical clusters during vitellogenesis. This ER reorganization requires Jagunal, which is an evolutionarily conserved ER membrane protein. Loss of Jagunal reduces vesicular traffic to the oocyte lateral membrane, but does not affect posterior polarized vesicular traffic, suggesting a role for Jagunal in facilitating vesicular traffic in the subcortex. Reduced membrane traffic caused by loss of Jagunal affects oocyte and bristle growth. We propose that ER reorganization is an important mechanism used by cells to prepare for an increased demand for membrane traffic, and Jagunal facilitates this process through ER clustering.

scholarly journals Cryo-EM structure of a proton-activated chloride channel TMEM206

2021 ◽  
Vol 7 (9) ◽  
pp. eabe5983
Author(s):  
Zengqin Deng ◽  
Yonghui Zhao ◽  
Jing Feng ◽  
Jingying Zhang ◽  
Haiyan Zhao ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Chloride Channels ◽  
Ion Selectivity ◽  
Chloride Ion ◽  
Transmembrane Segments ◽  
New Class ◽  
The Core ◽  
Cryo Electron Microscopy ◽  
Extracellular Region ◽  
Evolutionarily Conserved

TMEM206 has been recently identified as an evolutionarily conserved chloride channel that underlies ubiquitously expressed, proton-activated, outwardly rectifying anion currents. Here, we report the cryo–electron microscopy structure of pufferfish TMEM206, which forms a trimeric channel, with each subunit comprising two transmembrane segments and a large extracellular domain. An ample vestibule in the extracellular region is accessible laterally from the three side portals. The central pore contains multiple constrictions. A conserved lysine residue near the cytoplasmic end of the inner helix forms the presumed chloride ion selectivity filter. Unprecedentedly, the core structure and assembly closely resemble those of the epithelial sodium channel/degenerin family of sodium channels that are unrelated in amino acid sequence and conduct cations instead of anions. Together with electrophysiology, this work provides insights into ion conduction and gating for a new class of chloride channels that is architecturally distinct from previously characterized chloride channel families.

scholarly journals Cryo-EM structure of a proton-activated chloride channel TMEM206

2020 ◽  
Author(s):  
Zengqin Deng ◽  
Yonghui Zhao ◽  
Jing Feng ◽  
Jingying Zhang ◽  
Haiyan Zhao ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Chloride Channels ◽  
Ion Selectivity ◽  
Chloride Ion ◽  
Ion Conduction ◽  
Transmembrane Segments ◽  
New Class ◽  
Cryo Electron Microscopy ◽  
Extracellular Region ◽  
Evolutionarily Conserved

AbstractTMEM206 has been recently identified as an evolutionarily conserved chloride channel that underlies ubiquitously expressed, proton-activated, outwardly rectifying anion currents. Here we report the cryo-electron microscopy structure of pufferfish TMEM206, which forms a trimeric channel, with each subunit comprising two transmembrane segments, the outer and inner helices, and a large extracellular domain. An ample vestibule in the extracellular region is accessible laterally from the three side portals. The central pore contains multiple constrictions preventing ion conduction. A conserved lysine residue near the cytoplasmic end of the inner helix forms the presumed chloride ion selectivity filter. Unprecedentedly, the core structure and assembly closely resemble those of the epithelial sodium channel/degenerin family of sodium channels that are unrelated in amino acid sequence and conduct cations instead of anions. Together with electrophysiology, this work provides insights into ion conduction and gating for a new class of chloride channels that is architecturally distinct from previously characterized chloride channel families.

scholarly journals ORP5 localizes to ER–lipid droplet contacts and regulates the level of PI(4)P on lipid droplets

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Ximing Du ◽  
Linkang Zhou ◽  
Yvette Celine Aw ◽  
Hoi Yin Mak ◽  
Yanqing Xu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Lipid Droplets ◽  
Lipid Synthesis ◽  
Integral Membrane Protein ◽  
Normal Cells ◽  
Bilayer Membranes ◽  
Contact Sites ◽  
Evolutionarily Conserved ◽  
Phosphatidylinositol 4

Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in cellular metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. During LD biogenesis and growth, this monolayer of lipids expands by acquiring phospholipids from the endoplasmic reticulum (ER) through nonvesicular mechanisms. Here, in a mini-screen, we find that ORP5, an integral membrane protein of the ER, can localize to ER–LD contact sites upon oleate loading. ORP5 interacts with LDs through its ligand-binding domain, and ORP5 deficiency enhances neutral lipid synthesis and increases the size of LDs. Importantly, there is significantly more phosphatidylinositol-4-phosphate (PI(4)P) and less phosphatidylserine (PS) on LDs in ORP5-deficient cells than in normal cells. The increased presence of PI(4)P on LDs in ORP5-deficient cells requires phosphatidylinositol 4-kinase 2-α. Our results thus demonstrate the existence of PI(4)P on LDs and suggest that LD-associated PI(4)P may be primarily used by ORP5 to deliver PS to LDs.

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