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Self-Archiving for Articles in Subscription-Based Journals SUBMITTED VERSION Sunita A. Ramesh, Stephen D. Tyerman, Matthew Gilliham, Bo Xu γ-Aminobutyric acid (GABA) signalling in plants Cellular and Molecular Life Sciences, 2017; 74(9):1577-1603 © Springer International Publishing 2016 This is a pre-print of an article published in Few-Body Systems. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00018-016-2415-7 PERMISSIONS https://www.springer.com/gp/open-access/publication-policies/self-archiving-policy Self-archiving for articles in subscription-based journals Springer journals’ policy on preprint sharing. By signing the Copyright Transfer Statement you still retain substantial rights, such as self- archiving: Author(s) are permitted to self-archive a pre-print and an author’s accepted manuscript version of their Article. a. A pre-print is the author’s version of the Article before peer-review has taken place ("Pre-Print”). Prior to acceptance for publication, Author(s) retain the right to make a Pre-Print of their Article available on any of the following: their own personal, self- maintained website; a legally compliant pre-print server such as but not limited to arXiv and bioRxiv. Once the Article has been published, the Author(s) should update the acknowledgement and provide a link to the definitive version on the publisher’s website: “This is a pre-print of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI]”. 27 April 2020 http://hdl.handle.net/2440/124330 Cellular and Molecular Life Sciences γ-aminobutyric acid (GABA) signalling in plants --Manuscript Draft-- Manuscript Number: Full Title: γ-aminobutyric acid (GABA) signalling in plants Article Type: Invited review Corresponding Author: Bo Xu, Ph.D University of Adelaide - Waite Campus Glen Osmond, SA AUSTRALIA Corresponding Author Secondary Information: Corresponding Author's Institution: University of Adelaide - Waite Campus Corresponding Author's Secondary Institution: First Author: Sunita A Ramesh, Ph.D First Author Secondary Information: Order of Authors: Sunita A Ramesh, Ph.D Stephen D Tyerman, Ph.D Matthew Gilliham, Ph.D Bo Xu, Ph.D Order of Authors Secondary Information: Funding Information: Centre of Excellence in Plant Energy Prof. Stephen D Tyerman Biology, Australian Research Council A/Prof. Matthew Gilliham (CE140100008) University of Adelaide A/Prof. Matthew Gilliham (FT130100709) Abstract: The role of γ-Aminobutyric acid (GABA) as a signal in animals has been documented over the past 6 decades. In contrast, evidence that GABA is a signal in plants has only emerged in the last 15 years, and it was not until last year that a mechanism by which this could occur was identified - a plant 'GABA receptor' that inhibits anion passage through the Aluminium Activated Malate Transporter family of proteins (ALMTs). ALMTs are multigenic, expressed in different organs and present on different membranes. We propose GABA regulation of ALMT activity could function as a signal that modulates plant growth, development and stress response. In this review, we compare and contrast the plant 'GABA receptor' with mammalian GABAA receptors in terms of their molecular identity, structure, mode of action and signalling roles. We also explore the implications of the discovery that GABA modulates anion flux in plants, its role in signal transduction for the regulation of plant physiology, the possibility that there may be other GABA binding sites and regions in the ALMT proteins (eg amino acid residues such as arginine and tyrosine) and explore the potential interactions between GABA and other signalling molecules. Suggested Reviewers: Barry J Shelp, Ph.D Professor of Plant Agriculture, University of Guelph [email protected] Prof. Shelp is a well-known expertise in GABA research in plant biology Enrico Martinoia, Ph.D Professor, Universitat Zurich [email protected] Prof. Martinoia is an expert in the field of ion transport and plant physiology José Feijó, Ph.D Professor, University Maryland Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation [email protected] Prof. Feijó is a well-known researcher focusing on ion trasnport and amino acid signaling in plant developmental biology Sergey Shabala, Ph.D Professor, University of Tasmania [email protected] Prof. Shabala is an excellent scientist in biophysics and plant ion transport in abiotic stress tolerance Opposed Reviewers: Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Manuscript Click here to download Manuscript Ramesh_et_al_2016_CMLS_review_20160831.pdf Click here to view linked References 1 γ-aminobutyric acid (GABA) signalling in plants 1 2 2 3 Sunita A Ramesh1, Stephen D Tyerman1, Matthew Gilliham1, Bo Xu1* 3 4 4 5 1Plant Transport and Signalling Lab, ARC Centre of Excellence in Plant Energy Biology and School of 5 6 Agriculture, Food and Wine, University of Adelaide, Waite Research Institute, Glen Osmond, SA 5064, Australia 6 7 7 8 *author to correspond: [email protected] 8 9 9 10 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 1 63 64 65 11 Abstract 1 12 2 13 The role of γ-Aminobutyric acid (GABA) as a signal in animals has been documented over the past 6 decades. In 3 14 contrast, evidence that GABA is a signal in plants has only emerged in the last 15 years, and it was not until last 4 15 year that a mechanism by which this could occur was identified – a plant ‘GABA receptor’ that inhibits anion 5 16 passage through the Aluminium Activated Malate Transporter family of proteins (ALMTs). ALMTs are 6 17 multigenic, expressed in different organs and present on different membranes. We propose GABA regulation of 7 18 ALMT activity could function as a signal that modulates plant growth, development and stress response. In this 8 19 review, we compare and contrast the plant ‘GABA receptor’ with mammalian GABAA receptors in terms of their 9 20 molecular identity, structure, mode of action and signalling roles. We also explore the implications of the 10 21 discovery that GABA modulates anion flux in plants, its role in signal transduction for the regulation of plant 11 22 physiology, the possibility that there may be other GABA binding sites and regions in the ALMT proteins (eg 12 23 amino acid residues such as arginine and tyrosine) and explore the potential interactions between GABA and other 13 24 signalling molecules. 14 25 15 26 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 2 63 64 65 27 Keywords 1 28 γ-aminobutyric acid 2 29 Aluminium-activated malate transporters 3 30 GABAA receptors 4 31 Signalling 5 32 GABA metabolism 6 33 Carbon nitrogen balance 7 34 Stress response 8 35 Topology 9 36 Pharmacology 10 37 11 38 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 3 63 64 65 39 Abbreviations 1 40 2 3-MPA 3-mercaptopropionic acid 3 ALMT Aluminium (Al3+)-activated malate transporter 4 5 Cys Cysteine 6 EC50 Half-maximal response 7 8 F / Phe Phenylalanine 9 GABA γ-aminobutyric acid 10 GABA-T GABA transaminase 11 12 GABP GABA permease 13 GAD Glutamate decarboxylase 14 15 GAT GABA transporter 16 GDH Glutamate dehydrogenase 17 E / Glu Glutamic acid 18 19 I / Ile Isoleucine 20 SSA Succinic semialdehyde 21 22 SSADH Succinic semialdehyde dehydrogenase 23 T / Thr Threonine 24 D / Asp Aspartic acid 25 V / Val Valine 26 27 Y / Tyr Tyrosine 28 Q / Gln Glutamine 29 L / Leu Leucine 30 31 R / Arg Arginine 32 TMDs Transmembrane domains 33 K / Lys Lysine 34 S / Ser Serine 35 36 G /Gly Glycine 37 41 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 4 63 64 65 42 Introduction 1 43 2 44 The non-proteinogenic amino acid γ-aminobutyric acid (GABA) was first isolated in 1949 from potato tubers [1], 3 45 prior to its discovery in animal brain extracts [2]. Soon after, in the 1950s and 1960s, evidence was gathered that 4 46 suggested GABA might act as an inhibitory neurotransmitter in animals; GABA was found to suppress impulses 5 47 generated by crayfish stretch receptor neurons [3,4]. Yet, it was not until Bloom et al. (1971) that GABA was 6 48 localised to mammalian nerve terminals [5], and it took a further ten years until the mechanism by which GABA 7 49 acts as an inhibitory neurotransmitter was identified – via its activation of GABAA (ionotropic) and GABAB 8 50 (metabotropic) receptors [6]. In mammals, GABA counteracts the action of excitatory neurotransmitters in - 9 51 the mature brain [5], through the activation of a Cl conductance that passes through GABAA receptors into mature 10 52 neurons leading to membrane hyperpolarisation [7]. This prevents the neurons from firing and thus has a calming 11 53 effect [8]. Its action has been mainly described in the nervous system where GABA receptors regulate brain 12 54 function and development [9,10], although GABAergic receptors have also been described as functioning in other 13 55 tissues beyond neuronal cells, such as human organs [11,12].
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