scholarly journals Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Amanda H Lewis ◽  
Jörg Grandl
Keyword(s):  
Ion Channels ◽  
Cellular Membrane ◽  
Membrane Curvature ◽  
Membrane Tension ◽  
Mechanical Sensitivity ◽  
Physical Stimulus ◽  
Membrane Stretch ◽  
Channel Inactivation ◽  
Resting Tension ◽  
Membrane Geometry

Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent mechanical sensitivity of Piezo1 varies substantially across cellular environments, stimulating methods and protocols, raising the fundamental questions of what precise physical stimulus activates the channel and how its stimulus sensitivity is regulated. Here, we measured Piezo1 currents evoked by membrane stretch in three patch configurations, while simultaneously visualizing and measuring membrane geometry. Building on this approach, we developed protocols to minimize resting membrane curvature and tension prior to probing Piezo1 activity. We find that Piezo1 responds to lateral membrane tension with exquisite sensitivity as compared to other mechanically activated channels and that resting tension can drive channel inactivation, thereby tuning overall mechanical sensitivity of Piezo1. Our results explain how Piezo1 can function efficiently and with adaptable sensitivity as a sensor of mechanical stimulation in diverse cellular contexts.

Self-Assembly and Biogenesis of the Cellular Membrane are Dictated by Membrane Stretch and Composition

2019 ◽  
Vol 123 (32) ◽  
pp. 6997-7005 ◽  
Author(s):  
Akshata R. Naik ◽  
Eric R. Kuhn ◽  
Kenneth T. Lewis ◽  
Keith M. Kokotovich ◽  
Krishna R. Maddipati ◽  
...  
Keyword(s):  
Self Assembly ◽  
Cellular Membrane ◽  
Membrane Stretch

Ion-channel properties of mastoparan, a 14-residue peptide from wasp venom, and of MP3, a 12-residue analogue

1990 ◽  
Vol 239 (1296) ◽  
pp. 383-400 ◽  
Keyword(s):  
Ion Channels ◽  
Lipid Bilayers ◽  
Type I ◽  
Type Ii ◽  
Channel Formation ◽  
Channel Inactivation ◽  
Ion Channel Properties ◽  
Discrete Channel ◽  
Voltage Dependent ◽  
Channel Properties

Mastoparan, a 14-residue peptide, has been investigated with respect to its ability to form ion channels in planar lipid bilayers. In the presence of 0.3 - 3.0 μ M mastoparan, two types of activity are seen. Type I activity is characterized by discrete channel openings, exhibiting multiple con­ductance levels in the range 15-700 pS. Type II activity is characterized by transient increases in bilayer conductance, up to a maximum of about 650 pS. Both type I and type II activities are voltage dependent. Channel activation occurs if the compartment containing mastoparan is held at a positive potential; channel inactivation if the same compartment is held at a negative potential. Channel formation is dependent on ionic strength; channel openings are only observed at KCl concentrations of 0.3 M or above. Furthermore, raising the concentration of KCl to 3.0 M stabilizes the open form of the channel. Mastoparan channels are weakly cation selective, P K/Cl ≈ 2. A 12-residue analogue, des -Ile 1 , Asn 2 mastoparan, preferentially forms type I channels. The ion channels formed by these short peptides may be modelled in terms of bundles of transmembrane α -helices.

scholarly journals MscS-like Mechanosensitive Ion Channels: Modular Sensors and Reporters of Membrane Tension

2017 ◽  
Vol 112 (3) ◽  
pp. 38a
Author(s):  
Elizabeth Haswell ◽  
Debarati Basu ◽  
Eric S. Hamilton ◽  
Grigory Maksaev ◽  
Matthew Mixdorf ◽  
...  
Keyword(s):  
Ion Channels ◽  
Membrane Tension ◽  
Mechanosensitive Ion Channels

scholarly journals Active Regulation of Cellular Membrane Tension

2014 ◽  
Vol 106 (2) ◽  
pp. 705a
Author(s):  
Jiaxiang Tao ◽  
Sean X. Sun
Keyword(s):  
Cellular Membrane ◽  
Membrane Tension ◽  
Active Regulation

scholarly journals Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms

2020 ◽  
Author(s):  
Anna Pabis ◽  
Robert J. Rawle ◽  
Peter M. Kasson
Keyword(s):  
Viral Entry ◽  
Transmembrane Domain ◽  
Critical Role ◽  
Cellular Membrane ◽  
Membrane Curvature ◽  
Viral Envelope ◽  
Enveloped Viruses ◽  
Influenza Hemagglutinin ◽  
Hemagglutinin Protein ◽  
Dynamics Simulations

AbstractEnveloped viruses enter cells via a process of membrane fusion between the viral envelope and a cellular membrane. For influenza virus, mutational data have shown that the membrane-inserted portions of the hemagglutinin protein play a critical role in achieving fusion. In contrast to the relatively well-understood ectodomain, a predictive mechanistic understanding of the intramembrane mechanisms by which influenza hemagglutinin drives fusion has been elusive. We have used molecular dynamics simulations of fusion between a full-length hemagglutinin proteoliposome and a lipid bilayer to analyze these mechanisms. In our simulations, hemagglutinin first acts within the membrane to increase lipid tail protrusion and promote stalk formation and then acts to engage the distal leaflets of each membrane and promote stalk widening, curvature, and eventual fusion. These two sequential mechanisms, one occurring prior to stalk formation and one after, are consistent with experimental measurements we report of single-virus fusion kinetics to liposomes of different sizes. The resulting model also helps explain and integrate prior mutational and biophysical data, particularly the mutational sensitivity of the fusion peptide N-terminus and the length sensitivity of the transmembrane domain. We hypothesize that entry by other enveloped viruses may also utilize sequential processes of acyl tail exposure followed by membrane curvature and distal leaflet engagement.

scholarly journals Timing of ESCRT-III protein recruitment and membrane scission during HIV-1 assembly

2018 ◽  
Author(s):  
Daniel S. Johnson ◽  
Marina Bleck ◽  
Sanford M. Simon
Keyword(s):  
Multivesicular Body ◽  
Cellular Membrane ◽  
Membrane Curvature ◽  
Gag Protein ◽  
Endosomal Sorting ◽  
Membrane Scission ◽  
Nuclear Envelope Formation ◽  
Protein Recruitment ◽  
Late Domains ◽  
Hiv 1

The Endosomal Sorting Complexes Required for Transport III (ESCRT-III) proteins are critical for cellular membrane scission processes with topologies inverted relative to clathrin-mediated endocytosis. Some viruses appropriate ESCRT-IIIs for their release. By imaging single assembling viral-like particles of HIV-1, we observed that ESCRT-IIIs and the ATPase VPS4 arrive after most of the virion membrane is bent, linger for tens of seconds, and depart ∼20 seconds before scission. These observations suggest ESCRT-IIIs are recruited by a combination of membrane curvature and the late domains of the HIV-1 Gag protein. ESCRT-IIIs may pull the neck into a narrower form but must leave to allow scission. If scission does not occur within minutes of ESCRT departure, ESCRT-III and VPS4 are recruited again. This mechanistic insight is likely relevant for other ESCRT dependent scission processes including cell division, endosome tubulation, multivesicular body and nuclear envelope formation, and secretion of exosomes and ectosomes.

scholarly journals Complimentary action of structured and unstructured domains of epsin supports clathrin-mediated endocytosis at high tension

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jophin G. Joseph ◽  
Carlos Osorio ◽  
Vivian Yee ◽  
Ashutosh Agrawal ◽  
Allen P. Liu
Keyword(s):  
Lipid Bilayer ◽  
Adaptor Protein ◽  
Intrinsically Disordered Protein ◽  
Membrane Curvature ◽  
Membrane Tension ◽  
Intrinsically Disordered ◽  
Enth Domain ◽  
C Terminus ◽  
High Tension ◽  
Membrane Bending

AbstractMembrane tension plays an inhibitory role in clathrin-mediated endocytosis (CME) by impeding the transition of flat plasma membrane to hemispherical clathrin-coated structures (CCSs). Membrane tension also impedes the transition of hemispherical domes to omega-shaped CCSs. However, CME is not completely halted in cells under high tension conditions. Here we find that epsin, a membrane bending protein which inserts its N-terminus H0 helix into lipid bilayer, supports flat-to-dome transition of a CCS and stabilizes its curvature at high tension. This discovery is supported by molecular dynamic simulation of the epsin N-terminal homology (ENTH) domain that becomes more structured when embedded in a lipid bilayer. In addition, epsin has an intrinsically disordered protein (IDP) C-terminus domain which induces membrane curvature via steric repulsion. Insertion of H0 helix into lipid bilayer is not sufficient for stable epsin recruitment. Epsin’s binding to adaptor protein 2 and clathrin is critical for epsin’s association with CCSs under high tension conditions, supporting the importance of multivalent interactions in CCSs. Together, our results support a model where the ENTH and unstructured IDP region of epsin have complementary roles to ensure CME initiation and CCS maturation are unimpeded under high tension environments.

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