Journal article
Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family
The Journal of neuroscience, Vol.26(50), pp.13089-13101
12/13/2006
DOI: 10.1523/JNEUROSCI.2855-06.2006
PMCID: PMC6674967
PMID: 17167098
Abstract
Mints/X11s are adaptor proteins composed of three isoforms: neuron-specific Mints 1 and 2, and the ubiquitously expressed Mint 3. We have now analyzed constitutive and conditional knock-out mice for all three Mints/X11s. We found that approximately 80% of mice lacking both neuron-specific Mint isoforms (Mints 1 and 2) die at birth, whereas mice lacking any other combination of Mint isoforms survive normally. The approximately 20% surviving Mint 1/2 double knock-out mice exhibit a decrease in weight and deficits in motor behaviors. Hippocampal slice electrophysiology uncovered a decline in spontaneous neurotransmitter release, lowered synaptic strength, and enhanced paired-pulse facilitation in Mint-deficient mice, suggesting a decreased presynaptic release probability. Acute ablation of Mint expression in cultured neurons from conditional Mint 1/2/3 triple knock-in mice also revealed a decline in spontaneous release, confirming that deletion of Mints impair presynaptic function. Quantitation of synaptic proteins showed that acute deletion of Mints caused a selective increase in Munc18-1 and Fe65 proteins, and overexpression of Munc18-1 in wild-type neurons also produced a decrease in spontaneous release, suggesting that the interaction of Mints with Munc18-1 may contribute to the presynaptic phenotype observed in Mint-deficient mice. Our studies thus indicate that Mints are important regulators of presynaptic neurotransmitter release that are essential for mouse survival.
Details
- Title: Subtitle
- Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family
- Creators
- Angela Ho - Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111,USA. angela.ho@utsouthwestern.eduWade MorishitaDeniz AtasoyXinran LiuKatsuhiko TabuchiRobert E HammerRobert C MalenkaThomas C Südhof
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.26(50), pp.13089-13101
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.2855-06.2006
- PMID
- 17167098
- PMCID
- PMC6674967
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- F32-AG05844 / NIA NIH HHS R37 MH052804 / NIMH NIH HHS F32 AG005844 / NIA NIH HHS R37-MH52804-06 / NIMH NIH HHS
- Language
- English
- Date published
- 12/13/2006
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984040394702771
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