Molecular in situ topology of Aczonin/Piccolo and associated proteins at the mammalian neurotransmitter release site

Limbach, ChristophUppsala universitet,Institutionen för neurovetenskap,Molecular cell biology (author)

The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also for synaptic ontogeny and plasticity. However, its spatial organization in situ is virtually unknown. Aczonin/Piccolo is a putative organizer protein of mammalian active zones. We determined by immunogold electron microscopy (EM) (i) the spatial arrangement (i. e., topology) of 11 segments of the Aczonin polypeptide in situ, and correlated it to (ii) the positioning of Aczonin-interacting domains of Bassoon, CAST/ELKS, Munc13, and RIM and (iii) the ultrastructurally defined presynaptic macromolecular aggregates known as dense projections and synaptic ribbons. At conventional synapses, Aczonin assumes a compact molecular topology within a layer 35 to 80 nm parallel to the plasma membrane (PM), with a "trunk" sitting on the dense projection top and a C-terminal "arm" extending down toward the PM and sideward to the dense projection periphery. At ribbon synapses, Aczonin occupies the whole ribbon area. Bassoon colocalizes with Aczonin at conventional synapses but not at ribbon synapses. At both conventional and ribbon synapses, CAST, Munc13, and RIM are segregated from Aczonin, closer to the PM, and Aczonin is positioned such that it may control the access of neurotransmitter vesicles to the fusion site.

Laue, Michael M. (author)
Wang, Xiaolu (author)
Hu, Bin (author)
Thiede, NadineUppsala universitet,Molekylär cellbiologi (author)
Hultqvist, GretaUppsala universitet,Institutionen för neurovetenskap,Molekylär cellbiologi(Swepub:uu)grhul102 (author)
Kilimann, Manfred W.Uppsala universitet,Institutionen för neurovetenskap,Molekylär cellbiologi(Swepub:uu)makil021 (author)
Uppsala universitetInstitutionen för neurovetenskap (creator_code:org_t)

In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences108:31, s. E392-E4010027-84241091-6490

By the author/editor: Limbach, Christo ...; Laue, Michael M.; Wang, Xiaolu; Hu, Bin; Thiede, Nadine; Hultqvist, Greta; show more...; Kilimann, Manfre ...; show less...

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