Mapping axon initial segment structure and function by multiplexed proximity biotinylation
Autor: | Matthew N. Rasband, Christophe Leterrier, Juan A. Oses-Prieto, Brian C. Lim, Cameron Smith, Abhijeet R. Joshi, Matthias Koenning, Donna Palmer, Philip Ng, Hamdan Hamdan, Tomohiro Torii, Alma L. Burlingame |
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Přispěvatelé: | Alfaisal University, Baylor College of Medicine (BCM), Baylor University, Institut de neurophysiopathologie (INP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [San Francisco] (UCSF), University of California, NIH NS044916(MNR), NIH NS069688 (MNR), GM103481 (ALB), CNRS ATIP AO2016 (CL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC) |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Proteome 1.1 Normal biological development and functioning [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Science General Physics and Astronomy Molecular neuroscience Article General Biochemistry Genetics and Molecular Biology Mass Spectrometry Rats Sprague-Dawley 03 medical and health sciences Mice 0302 clinical medicine Microtubule Underpinning research Organelle Animals Humans Biotinylation lcsh:Science Axon Initial Segment Neurons Multidisciplinary NDEL1 Chemistry Neurosciences General Chemistry Axon initial segment Fusion protein Cellular neuroscience Axons Transport protein Cell biology Rats Protein Transport 030104 developmental biology nervous system lcsh:Q Sprague-Dawley 030217 neurology & neurosurgery |
Zdroj: | Nature communications, vol 11, iss 1 Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) Nature Communications Nature Communications, Nature Publishing Group, 2020, 11 (1), ⟨10.1038/s41467-019-13658-5⟩ Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-019-13658-5⟩ BASE-Bielefeld Academic Search Engine |
ISSN: | 2041-1723 |
Popis: | Axon initial segments (AISs) generate action potentials and regulate the polarized distribution of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na+ and K+ channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compartments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons. The axon initial segment (AIS) is a specialized location in neurons with clustered ion channels which regulates the distribution of neuronal materials. Here, the authors use proximity biotinylation to examine the AIS proteome and better define its molecular organization. |
Databáze: | OpenAIRE |
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