Sensing bilayer tension: bacterial mechanosensitive channels and their gating mechanisms

Abstract

Mechanosensitive channels sense and respond to changes in bilayer tension. In many respects, this is a unique property: the changes in membrane tension gate the channel, leading to the transient formation of open non-selective pores. Pore diameter is also high for the bacterial channels studied, MscS and MscL. Consequently, in cells, gating has severe consequences for energetics and homoeostasis, since membrane depolarization and modification of cytoplasmic ionic composition is an immediate consequence. Protection against disruption of cellular integrity, which is the function of the major channels, provides a strong evolutionary rationale for possession of such disruptive channels. The elegant crystal structures for these channels has opened the way to detailed investigations that combine molecular genetics with electrophysiology and studies of cellular behaviour. In the present article, the focus is primarily on the structure of MscS, the small mechanosensitive channel. The description of the structure is accompanied by discussion of the major sites of channel-lipid interaction and reasoned, but limited, speculation on the potential mechanisms of tension sensing leading to gating.

Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS

“…2C). Together, these results indicate that the molecular mechanism underlying the mechanosensitivity of MscS and MscL differs for the two channels in accordance with several previous reports (19)(20)(21)(22).…”

Recent characterizations of MscS and its homologs provide insight into the basis of ion selectivity in mechanosensitive channels

“…A particularly productive model system for the study of MS channel structure and function has been the Mechanosensitive channel of Small conductance (MscS), one of several channels discovered in the inner membrane of Escherichia coli giant spheroplasts. 3 MscS is a weakly anion-selective [4][5][6][7] ion channel, gated directly through tension in the membrane. When bacterial cells are subjected to hypoosmotic stress, cellular swelling increases membrane tension, which gates MscS and a second MS channel called MscL (Large conductance).…”

“…3,24,25 They share a slight conductance asymmetry under opposite membrane potentials, both exhibiting larger conductances under negative membrane potentials. Like EcMscS, MSL10 activation does not depend on the sign of membrane curvature and is easily observed both under positive and negative membrane potentials.…”

“…27 However, MSL10 differs from MscS in several key aspects. 3,24,25 Though both channels are mechanosensitive, their tension-dependent gating results in different single-channel conductances: approximately 300 pS for EcMscS and intriguing family of proteins. The wealth of information regarding the structure and function of EcMscS provides a solid basis for the interpretation of these data.…”

Recent Advances in Membrane Biochemistry

“…This method has recently been used to produce a number of keenly anticipated structures detailing the conformational changes that accompany ligand binding to receptors [4,5] Delegates at the Symposium were entertained and educated by presentations covering a wide range of high-resolution structures encompassing the whole gamut of membrane protein types, including channels, transporters and receptors, in both the poster sessions and the oral presentations. Ian Booth and his group provided a detailed description of the structure of the mechanosensitive channel MscS that is responsible for monitoring and responding to bilayer tension to ensure cellular integrity when bacteria are subjected to hypoosmotic stress [6]. The relationship between the channel and its lipid environment and the mechanism by which lipid tension is coupled to gate opening were also examined.…”