Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at http://www.ucl.ac.uk/finance/research/post_award/post_award_contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Abrogating Munc18-1-SNARE complex interaction has limited impact on exocytosis in PC12 cells.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Malintan NT, Nguyen TH, Han L, Latham CF, Osborne SL, Wen PJ, Lim SJT, Sugita S, Collins BM, Meunier FA
  • Publication date:
  • Pagination:
    21637, 21646
  • Journal:
    J Biol Chem
  • Volume:
  • Issue:
  • Status:
  • Country:
    United States
  • Print ISSN:
  • PII:
  • Language:
  • Keywords:
    Amino Acid Motifs, Amino Acid Sequence, Animals, Calcium, Exocytosis, Models, Biological, Molecular Conformation, Molecular Sequence Data, Munc18 Proteins, PC12 Cells, Protein Structure, Tertiary, Qa-SNARE Proteins, Rats, Recombinant Proteins, SNARE Proteins
Neuronal communication relies on the fusion of neurotransmitter-containing vesicles with the plasma membrane. The soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) proteins initiate membrane fusion through the formation of the SNARE complex, a process tightly regulated by Sec1/Munc18-1 (SM) proteins. The emerging trend is that SM proteins promote SNARE-mediated membrane fusion by binding to a Syntaxin N-terminal motif. Here we report that mutations in the hydrophobic pocket of Munc18-1 (F115E and E132A), predicted to disrupt the N-terminal Sx1a interaction have a modest effect on binding to Sx1a in its free state, but abolish binding to the SNARE complex. Overexpression of the Munc18-1 mutant in PC12 cells lacking Munc18-1 rescues both neuroexocytosis and the plasma membrane localization of Syntaxin. However, total internal reflection fluorescence microscopy analysis reveals that expression of a Munc18-1 double mutant reduces the rate of vesicle fusion, an effect only detectable at the onset of stimulation. The Munc18-1 hydrophobic pocket is therefore critical for SNARE complex binding. However, mutations abrogating this interaction have a limited impact on Ca(2+)-dependent exocytosis in PC12 cells.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
There are no UCL People associated with this publication
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by