RIM proteins tether Ca2+ channels to presynaptic active zones via a direct PDZ-domain interaction

Pascal S. Kaeser, Lunbin Deng, Yun Wang, Irina Dulubova, Xinran Liu, Jose Rizo-Rey, Thomas C. Südhof

Research output: Contribution to journalArticle

294 Scopus citations

Abstract

At a synapse, fast synchronous neurotransmitter release requires localization of Ca2+ channels to presynaptic active zones. How Ca2+ channels are recruited to active zones, however, remains unknown. Using unbiased yeast two-hybrid screens, we here identify a direct interaction of the central PDZ domain of the active-zone protein RIM with the C termini of presynaptic N- and P/Q-type Ca2+ channels but not L-type Ca2+ channels. To test the physiological significance of this interaction, we generated conditional knockout mice lacking all multidomain RIM isoforms. Deletion of RIM proteins ablated most neurotransmitter release by simultaneously impairing the priming of synaptic vesicles and by decreasing the presynaptic localization of Ca2+ channels. Strikingly, rescue of the decreased Ca2+-channel localization required the RIM PDZ domain, whereas rescue of vesicle priming required the RIM N terminus. We propose that RIMs tether N- and P/Q-type Ca2+ channels to presynaptic active zones via a direct PDZ-domain-mediated interaction, thereby enabling fast, synchronous triggering of neurotransmitter release at a synapse.

Original languageEnglish (US)
Pages (from-to)282-295
Number of pages14
JournalCell
Volume144
Issue number2
DOIs
StatePublished - Jan 21 2011

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this