TY - JOUR
T1 - Reduced dynamin-1 levels in neurons lacking MUNC18-1
AU - Lammertse, Hanna C. A.
AU - Moro, Alessandro
AU - Saarloos, Ingrid
AU - Toonen, Ruud F.
AU - Verhage, Matthijs
N1 - Funding Information: This work was supported by a European Research Council (ERC) Advanced grant (322966) of the European Union (to M.V.), COSYN (Comorbidity and Synapse Biology in Clinically Overlapping Psychiatric Disorders; Horizon 2020 Framework Programme of the European Union under RIA grant agreement 667301 to M.V.) and Lundbeckfonden (R277-2018-802 to M.V.). Open access funding provided by Vrije Universiteit Amsterdam. Deposited in PMC for immediate release. Publisher Copyright: © 2022. Published by The Company of Biologists Ltd.
PY - 2022/11/15
Y1 - 2022/11/15
N2 - MUNC18-1 (also known as syntaxin-binding protein-1, encoded by Stxbp1) binds to syntaxin-1. Together, these proteins regulate synaptic vesicle exocytosis and have a separate role in neuronal viability. In Stxbp1 null mutant neurons, syntaxin-1 protein levels are reduced by 70%. Here, we show that dynamin-1 protein levels are reduced at least to the same extent, and transcript levels of Dnm1 (which encodes dynamin-1) are reduced by 50% in Stxbp1 null mutant brain. Several, but not all, other endocytic proteins were also found to be reduced, but to a lesser extent. The reduced dynamin-1 expression was not observed in SNAP25 null mutants or in double-null mutants of MUNC13-1 and -2 (also known as Unc13a and Unc13b, respectively), in which synaptic vesicle exocytosis is also blocked. Co-immunoprecipitation experiments demonstrated that dynamin-1 and MUNC18-1 do not bind directly. Furthermore, MUNC18-1 levels were unaltered in neurons lacking all three dynamin paralogues. Finally, overexpression of dynamin-1 was not sufficient to rescue neuronal viability in Stxbp1 null mutant neurons; thus, the reduction in dynamin-1 is not the single cause of neurodegeneration of these neurons. The reduction in levels of dynamin-1 protein and mRNA, as well as of other endocytosis proteins, in Stxbp1 null mutant neurons suggests that MUNC18-1 directly or indirectly controls expression of other presynaptic genes.
AB - MUNC18-1 (also known as syntaxin-binding protein-1, encoded by Stxbp1) binds to syntaxin-1. Together, these proteins regulate synaptic vesicle exocytosis and have a separate role in neuronal viability. In Stxbp1 null mutant neurons, syntaxin-1 protein levels are reduced by 70%. Here, we show that dynamin-1 protein levels are reduced at least to the same extent, and transcript levels of Dnm1 (which encodes dynamin-1) are reduced by 50% in Stxbp1 null mutant brain. Several, but not all, other endocytic proteins were also found to be reduced, but to a lesser extent. The reduced dynamin-1 expression was not observed in SNAP25 null mutants or in double-null mutants of MUNC13-1 and -2 (also known as Unc13a and Unc13b, respectively), in which synaptic vesicle exocytosis is also blocked. Co-immunoprecipitation experiments demonstrated that dynamin-1 and MUNC18-1 do not bind directly. Furthermore, MUNC18-1 levels were unaltered in neurons lacking all three dynamin paralogues. Finally, overexpression of dynamin-1 was not sufficient to rescue neuronal viability in Stxbp1 null mutant neurons; thus, the reduction in dynamin-1 is not the single cause of neurodegeneration of these neurons. The reduction in levels of dynamin-1 protein and mRNA, as well as of other endocytosis proteins, in Stxbp1 null mutant neurons suggests that MUNC18-1 directly or indirectly controls expression of other presynaptic genes.
KW - Dynamin
KW - Endocytosis
KW - Exocytosis
KW - MUNC18-1
KW - Presynaptic genes
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U2 - https://doi.org/10.1242/jcs.260132
DO - https://doi.org/10.1242/jcs.260132
M3 - Article
C2 - 36245272
SN - 0021-9533
VL - 135
SP - 1
EP - 12
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 22
M1 - jcs260132
ER -