Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains

Cornelia J Geerts, Roberta Mancini, Ning Chen, Frank T W Koopmans, Ka Wan Li, August B Smit, Jan R T van Weering, Matthijs Verhage, Alexander J A Groffen

Research output: Contribution to JournalArticleAcademicpeer-review


The secretory pathway in neurons requires efficient targeting of cargos and regulatory proteins to their release sites. Tomosyn contributes to synapse function by regulating synaptic vesicle (SV) and dense-core vesicle (DCV) secretion. While there is large support for the presynaptic accumulation of tomosyn in fixed preparations, alternative subcellular locations have been suggested. Here we studied the dynamic distribution of tomosyn-1 (Stxbp5) and tomosyn-2 (Stxbp5l) in mouse hippocampal neurons and observed a mixed diffuse and punctate localization pattern of both isoforms. Tomosyn-1 accumulations were present in axons and dendrites. As expected, tomosyn-1 was expressed in about 75% of the presynaptic terminals. Interestingly, also bidirectional moving tomosyn-1 and -2 puncta were observed. Despite the lack of a membrane anchor these puncta co-migrated with synapsin and neuropeptide Y, markers for respectively SVs and DCVs. Genetic blockade of two known tomosyn interactions with synaptotagmin-1 and its cognate SNAREs did not abolish its vesicular co-migration, suggesting an interplay of protein interactions mediated by the WD40 and SNARE domains. We hypothesize that the vesicle-binding properties of tomosyns may control the delivery, pan-synaptic sharing and secretion of neuronal signaling molecules, exceeding its canonical role at the plasma membrane.

Original languageEnglish
Article numbere0180912
Pages (from-to)e0180912
JournalPLoS ONE
Issue number7
Publication statusPublished - 2017


  • Animals
  • Axons
  • Binding Sites
  • Blotting, Western
  • Cells, Cultured
  • Dendrites
  • Hippocampus
  • Journal Article
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Microscopy, Immunoelectron
  • Nerve Tissue Proteins
  • Neurons
  • Neuropeptide Y
  • Presynaptic Terminals
  • Protein Binding
  • Protein Transport
  • R-SNARE Proteins
  • Secretory Vesicles
  • Synapsins
  • Synaptic Vesicles
  • Synaptotagmin I


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