LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons
Publication Date
July 18, 2016
Journal
PLOS Biology
Authors
Seok Kyu Kwon, Richard Sando Iii, Tommy L. Lewis, Yusuke Hirabayashi, et al
Volume
14
Issue
7
Pages
e1002516
DOI
https://dx.plos.org/10.1371/journal.pbio.1002516
Publisher URL
http://journals.plos.org/plosbiology/article?id=10.1371%2Fjournal.pbio.1002516
Web of Science
000380768700012
Scopus
84980615080
Mendeley
http://www.mendeley.com/research/lkb1-regulates-mitochondriadependent-presynaptic-calcium-clearance-neurotransmitter-release-properti
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Mendeley | Further Information

{"title"=>"LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons", "type"=>"journal", "authors"=>[{"first_name"=>"Seok Kyu", "last_name"=>"Kwon", "scopus_author_id"=>"57199820272"}, {"first_name"=>"Richard", "last_name"=>"Sando", "scopus_author_id"=>"54956422100"}, {"first_name"=>"Tommy L.", "last_name"=>"Lewis", "scopus_author_id"=>"15765830300"}, {"first_name"=>"Yusuke", "last_name"=>"Hirabayashi", "scopus_author_id"=>"8246828000"}, {"first_name"=>"Anton", "last_name"=>"Maximov", "scopus_author_id"=>"7005154773"}, {"first_name"=>"Franck", "last_name"=>"Polleux", "scopus_author_id"=>"6603365364"}], "year"=>2016, "source"=>"PLoS Biology", "identifiers"=>{"pui"=>"611573157", "sgr"=>"84982854167", "issn"=>"15457885", "pmid"=>"27429220", "scopus"=>"2-s2.0-84982854167", "doi"=>"10.1371/journal.pbio.1002516", "isbn"=>"1544-9173"}, "id"=>"ef31e988-3019-3a40-910b-0d025e675a50", "abstract"=>"Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca 2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca 2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca 2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demon-strate that the presence or absence of mitochondria at presynaptic boutons dictates neuro-transmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca 2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca 2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca 2+ uptake at glutamater-gic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mecha-nisms whereby mitochondria control neurotransmitter release properties in a bouton-spe-cific way through presynaptic Ca 2+ clearance. Author Summary Mitochondria perform many important biological functions, ranging from ATP produc-tion through oxidative phosphorylation to calcium clearance and lipid biosynthesis. In neurons of the mammalian cerebral cortex, we discovered that only ~50% of presynaptic boutons (the site where neurotransmission occurs) are associated with mitochondria while ~50% are not. Our results demonstrate that the presence of a presynaptic mitochondria plays a key role in calcium homeostasis and, thereby, regulates the properties of Funding: This work was supported by NIH-NS089456-06A1 (FP), NIH-F31MH094059 (RS), Human Frontier Science Program long-term fellowship (SKK), NIH-F32NS080464 (TLL) and NIH-NS087026 (AM), and an award from the Fondation Roger de Spoelberch (FP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. neurotransmitter release. We identify a protein kinase called LKB1, which regulates the ability of presynaptic mitochondria to clear calcium, by controlling the abundance of the mitochondrial calcium uniporter—a Ca 2+ -selective ion channel located in the mitochon-dria's inner membrane. Our results suggest that mitochondrial capture at individual pre-synaptic boutons along cortical axon plays a synapse-specific role in regulating neurotransmission through the ability to regulate presynaptic calcium homeostasis.", "link"=>"http://www.mendeley.com/research/lkb1-regulates-mitochondriadependent-presynaptic-calcium-clearance-neurotransmitter-release-properti", "reader_count"=>48, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>14, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>5, "Other"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>14, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>5, "Other"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>10, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>1, "Neuroscience"=>17, "Physics and Astronomy"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>17}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Portugal"=>1, "Germany"=>1}, "group_count"=>0}

Scopus | Further Information

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