Biophysical Reviews

, Volume 11, Issue 3, pp 327–333 | Cite as

“Force-From-Lipids” mechanosensation in Corynebacterium glutamicum

  • Yoshitaka Nakayama
  • Ken-ichi Hashimoto
  • Hisashi Kawasaki
  • Boris MartinacEmail author


Since the mechanosensitive channel MscCG has been identified as the major glutamate efflux system in Corynebacterium glutamicum, studies of mechanotransduction processes in this bacterium have helped to unpuzzle a long-unresolved mystery of glutamate efflux that has been utilised for industrial monosodium glutamate production. The patch clamp recording from C. glutamicum giant spheroplasts revealed the existence of three types of mechanosensitive (MS) channels in the cell membrane of this bacterium. The experiments demonstrated that the MS channels could be activated by membrane tension, indicating that the channel gating by mechanical force followed the “Force-From-Lipids (FFL)” principle characteristic of ion channels inherently sensitive to transbilayer pressure profile changes in the mechanically stressed membrane bilayer. Mechanical properties of the C. glutamicum membrane are characteristics of very soft membranes, which in the C. glutamicum membrane are due to negatively charged lipids as its exclusive constituents. Given that membrane lipids are significantly altered during the fermentation process in the monosodium glutamate production, MS channels seem to respond to changes in force transmission through the membrane bilayer due to membrane lipid dynamics. In this review, we describe the recent results describing corynebacterial FFL-dependent mechanosensation originating from the particular lipid composition of the C. glutamicum membrane and unique structure of MscCG-type channels.


NCgl1221 MscS Mechanosensation Glutamate efflux Fatty acid synthesis 



We acknowledge the Japanese Society for Promotion of Science (JSPS) for a fellowship to YN and the National Health and Medical Research Council of Australia for a Principal Research Fellowship to BM.

Author contributions

YN and BM wrote the manuscript. YN, HK, KH, and BM contributed to editing.

Compliance with ethical standards

Conflict of interest

Yoshitaka Nakayama declares that he has no conflict of interest. Ken-ichi Hashimoto declares that he has no conflict of interest. Hisashi Kawasaki declares that he has no conflict of interest. Boris Martinac declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Bansal-Mutalik R, Nikaido H (2011) Quantitative lipid composition of cell envelopes of Corynebacterium glutamicum elucidated through reverse micelle extraction. Proc Natl Acad Sci U S A 108:15360–15365. CrossRefGoogle Scholar
  2. Bavi O, Cox CD, Vossoughi M, Naghdabadi R, Jamali Y, Martinac B (2016) Influence of global and local membrane curvature on mechanosensitive ion channels: a finite element approach. Membranes (Basel) 6.
  3. Becker M, Boerngen K, Nomura T, Battle AR, Marin K, Martinac B, Kramer R (2013) Glutamate efflux mediated by Corynebacterium glutamicum MscCG, Escherichia coli MscS, and their derivatives. Biochim Biophys Acta 1828:1230–1240. CrossRefGoogle Scholar
  4. Boer M, Anishkin A, Sukharev S (2011) Adaptive MscS gating in the osmotic permeability response in E. coli: the question of time. Biochemistry 50:4087–4096. CrossRefGoogle Scholar
  5. Booth IR, Blount P (2012) The MscS and MscL families of mechanosensitive channels act as microbial emergency release valves. J Bacteriol 194:4802–4809. CrossRefGoogle Scholar
  6. Boerngen K, Battle AR, Moker N, Morbach S, Marin K, Martinac B, Kramer R (2010) The properties and contribution of the Corynebacterium glutamicum MscS variant to fine-tuning of osmotic adaptation. Biochim Biophys Acta 1798:2141–2149. CrossRefGoogle Scholar
  7. Boyd KJ, Alder NN, May ER (2017) Buckling under pressure: curvature-based lipid segregation and stability modulation in cardiolipin-containing bilayers. Langmuir 33:6937–6946. CrossRefGoogle Scholar
  8. Cantor RS (1999) Lipid composition and the lateral pressure profile in bilayers. Biophys J 76:2625–2639CrossRefGoogle Scholar
  9. Chiaradia L et al (2017) Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane. Sci Rep 7:12807. CrossRefGoogle Scholar
  10. Clausen MV, Jarerattanachat V, Carpenter EP, Sansom MSP, Tucker SJ (2017) Asymmetric mechanosensitivity in a eukaryotic ion channel. Proc Natl Acad Sci U S A 114:E8343–E8351. CrossRefGoogle Scholar
  11. Cox CD, Nakayama Y, Nomura T, Martinac B (2015) The evolutionary ‘tinkering’ of MscS-like channels: generation of structural and functional diversity. Pflügers Arch – Eur J Physiol 467(1):3–13CrossRefGoogle Scholar
  12. Cox CD et al (2016) Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nat Commun 7:10366. CrossRefGoogle Scholar
  13. Cox CD, Bavi N, Martinac B (2018) Bacterial mechanosensors. Annu Rev Physiol 80:71–93. CrossRefGoogle Scholar
  14. Edwards MD, Booth IR, Miller S (2004) Gating the bacterial mechanosensitive channels: MscS a new paradigm? Curr Opin Microbiol 7:163–167. CrossRefGoogle Scholar
  15. Eggeling L, Krumbach K, Sahm H (2001) l-Glutamate efflux with Corynebacterium glutamicum: why is penicillin treatment or Tween addition doing the same? J Mol Microbiol Biotechnol 3:67–68Google Scholar
  16. Elias-Wolff F, Linden M, Lyubartsev AP, Brandt EG (2019) Curvature sensing by cardiolipin in simulated buckled membranes. Soft Matter 15:792–802. CrossRefGoogle Scholar
  17. Guo YR, MacKinnon R (2017) Structure-based membrane dome mechanism for Piezo mechanosensitivity. eLife 6.
  18. Gustin MC, Zhou X-L, Martinac B, Kung C (1988) A mechanosensitive ion channel in the yeast plasma membrane. Science 242:762–765CrossRefGoogle Scholar
  19. Gutmann M, Hoischen C, Kramer R (1992) Carrier-mediated glutamate secretion by Corynebacterium glutamicum under biotin limitation. Biochim Biophys Acta 1112:115–123CrossRefGoogle Scholar
  20. Hashimoto K et al (2006) Changes in composition and content of mycolic acids in glutamate-overproducing Corynebacterium glutamicum. Biosci Biotechnol Biochem 70:22–30CrossRefGoogle Scholar
  21. Hashimoto K, Nakamura K, Kuroda T, Yabe I, Nakamatsu T, Kawasaki H (2010) The protein encoded by NCgl1221 in Corynebacterium glutamicum functions as a mechanosensitive channel. Biosci Biotechnol Biochem 74:2546–2549. CrossRefGoogle Scholar
  22. Hashimoto K, Murata J, Konishi T, Yabe I, Nakamatsu T, Kawasaki H (2012) Glutamate is excreted across the cytoplasmic membrane through the NCgl1221 channel of Corynebacterium glutamicum by passive diffusion. Biosci Biotechnol Biochem 76:1422–1424. CrossRefGoogle Scholar
  23. Hoischen C, Kramer R (1990) Membrane alteration is necessary but not sufficient for effective glutamate secretion in Corynebacterium glutamicum. J Bacteriol 172:3409–3416CrossRefGoogle Scholar
  24. Hurst AC, Petrov E, Kloda A, Nguyen T, Hool L, Martinac B (2008) MscS, the bacterial mechanosensitive channel of small conductance. Int J Biochem Cell Biol 40:581–585. CrossRefGoogle Scholar
  25. Kimura E, Abe C, Kawahara Y, Nakamatsu T, Tokuda H (1997) A dtsR gene-disrupted mutant of Brevibacterium lactofermentum requires fatty acids for growth and efficiently produces l-glutamate in the presence of an excess of biotin. Biochem Biophys Res Commun 234:157–161. CrossRefGoogle Scholar
  26. Kimura E, Yagoshi C, Kawahara Y, Ohsumi T, Nakamatsu T, Tokuda H (1999) Glutamate overproduction in Corynebacterium glutamicum triggered by a decrease in the level of a complex comprising DtsR and a biotin-containing subunit. Biosci Biotechnol Biochem 63:1274–1278. CrossRefGoogle Scholar
  27. Kinoshita S, Udaka S, Shimono M (1957) Studies on the amino acid fermentation part I. Production of l-glutamic acid by various microorganisms. J Gen Appl Microbiol 3:193–205. CrossRefGoogle Scholar
  28. Klatt S et al (2018) Identification of novel lipid modifications and intermembrane dynamics in Corynebacterium glutamicum using high-resolution mass spectrometry. J Lipid Res 59:1190–1204. CrossRefGoogle Scholar
  29. Kloda A, Martinac B (2002) Common evolutionary origins of mechanosensitive ion channels in Archaea, Bacteria and cell-walled Eukarya. Archaea 1:35–44CrossRefGoogle Scholar
  30. Levina N, Totemeyer S, Stokes NR, Louis P, Jones MA, Booth IR (1999) Protection of Escherichia coli cells against extreme turgor by activation of MscS and MscL mechanosensitive channels: identification of genes required for MscS activity. EMBO J 18:1730–1737. CrossRefGoogle Scholar
  31. Liang X, Howard J (2018) Structural biology: Piezo senses tension through curvature. Curr Biol 28:R357–R359. CrossRefGoogle Scholar
  32. Malcolm HR, Maurer JA (2012) The mechanosensitive channel of small conductance (MscS) superfamily: not just mechanosensitive channels anymore. Chembiochem 13:2037–2043. CrossRefGoogle Scholar
  33. Marshavina ZV, Gazaryan VA (1975) Effect of oleic acid and Tween-80 on lysine synthesis by the culture Corynebacterium glutamicum. Prikl Biokhim Mikrobiol 11:356–361Google Scholar
  34. Martinac B, Buechner M, Delcour AH, Adler J, Kung C (1987) Pressure-sensitive ion channel in Escherichia coli. Proc Natl Acad Sci U S A 84:2297–2301CrossRefGoogle Scholar
  35. Martinac B, Adler J, Kung C (1990) Mechanosensitive ion channels of E. coli activated by amphipaths. Nature 348:261–263. CrossRefGoogle Scholar
  36. Martinac B et al (2018) Tuning ion channel mechanosensitivity by asymmetry of the transbilayer pressure profile. Biophys Rev 10:1377–1384. CrossRefGoogle Scholar
  37. Nakamura J, Hirano S, Ito H, Wachi M (2007) Mutations of the Corynebacterium glutamicum NCgl1221 gene, encoding a mechanosensitive channel homolog, induce l-glutamic acid production. Appl Environ Microbiol 73:4491–4498. CrossRefGoogle Scholar
  38. Nakayama Y, Hashimoto KI, Sawada Y, Sokabe M, Kawasaki H, Martinac B (2018a) Corynebacterium glutamicum mechanosensitive channels: towards unpuzzling “glutamate efflux” for amino acid production. Biophys Rev 10:1359–1369. CrossRefGoogle Scholar
  39. Nakayama Y, Komazawa K, Bavi N, Hashimoto KI, Kawasaki H, Martinac B (2018b) Evolutionary specialization of MscCG, an MscS-like mechanosensitive channel, in amino acid transport in Corynebacterium glutamicum. Sci Rep 8:12893. CrossRefGoogle Scholar
  40. Nampoothiri KM et al (2002) Expression of genes of lipid synthesis and altered lipid composition modulates l-glutamate efflux of Corynebacterium glutamicum. Appl Microbiol Biotechnol 58:89–96CrossRefGoogle Scholar
  41. Nomura T et al (2012) Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS. Proc Natl Acad Sci U S A 109:8770–8775. CrossRefGoogle Scholar
  42. Oliver PM, Crooks JA, Leidl M, Yoon EJ, Saghatelian A, Weibel DB (2014) Localization of anionic phospholipids in Escherichia coli cells. J Bacteriol 196:3386–3398. CrossRefGoogle Scholar
  43. Perozo E, Kloda A, Cortes DM, Martinac B (2002) Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating. Nat Struct Biol 9(9):696–703CrossRefGoogle Scholar
  44. Phillips R, Ursell T, Wiggins P, Sens P (2009) Emerging roles for lipids in shaping membrane-protein function. Nature 459:379–385. CrossRefGoogle Scholar
  45. Ridone P, Grage SL, Patkunarajah A, Battle AR, Ulrich AS, Martinac B (2018) “Force-from-lipids” gating of mechanosensitive channels modulated by PUFAs. J Mech Behav Biomed Mater 79:158–167. CrossRefGoogle Scholar
  46. Shaikh S, Cox CD, Nomura T, Martinac B (2014) Energetics of gating MscS by membrane tension in azolectin liposomes and giant spheroplasts. Channels 8(4):321–326CrossRefGoogle Scholar
  47. Shiio I, Otsuka SI, Takahashi M (1962) Effect of biotin on the bacterial formation of glutamic acid. I. Glutamate formation and cellular premeability of amino acids. J Biochem 51:56–62CrossRefGoogle Scholar
  48. Sokabe M, Sachs F, Jing ZQ (1991) Quantitative video microscopy of patch clamped membranes stress, strain, capacitance, and stretch channel activation. Biophys J 59:722–728. CrossRefGoogle Scholar
  49. Sukharev SI, Blount P, Martinac B, Guy HR, Kung C (1996) MscL: a mechanosensitive channel in Escherichia coli. Soc Gen Physiol Ser 51:133–141Google Scholar
  50. Sukharev SI, Sigurdson WJ, Kung C, Sachs F (1999) Energetic and spatial parameters for gating of the bacterial large conductance mechanosensitive channel, MscL. J Gen Physiol 113:525–540CrossRefGoogle Scholar
  51. Teng J, Loukin S, Anishkin A, Kung C (2015) The force-from-lipid (FFL) principle of mechanosensitivity, at large and in elements. Pflugers Arch 467:27–37. CrossRefGoogle Scholar
  52. Udaka S (1960) Screening method for microorganisms accumulating metabolites and its use in the isolation of Micrococcus glutamicus. J Bacteriol 79:754–755Google Scholar
  53. Wang Y et al (2018) A novel Corynebacterium glutamicum l-glutamate exporter. Appl Environ Microbiol 84.
  54. Wilson ME, Maksaev G, Haswell ES (2013) MscS-like mechanosensitive channels in plants and microbes. Biochemistry 52:5708–5722. CrossRefGoogle Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Molecular Cardiology and Biophysics DivisionVictor Chang Cardiac Research InstituteDarlinghurstAustralia
  2. 2.Biotechnology Research CenterThe University of TokyoTokyoJapan
  3. 3.Collaborative Research Institute for Innovative MicrobiologyThe University of TokyoTokyoJapan
  4. 4.St Vincent’s Clinical School, Faculty of MedicineUniversity of New South WalesDarlinghurstAustralia

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