Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains.
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5529015?pdf=render |
| _version_ | 1819048490657906688 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Cornelia J Geerts |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T11:17:05Z |
| format | Article |
| id | doaj.art-aaa47e4ef143401f9fd51374439a4dba |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T11:17:05Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-aaa47e4ef143401f9fd51374439a4dba2022-12-21T19:05:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018091210.1371/journal.pone.0180912Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains.Cornelia J GeertsRoberta ManciniNing ChenFrank T W KoopmansKa Wan LiAugust B SmitJan R T van WeeringMatthijs VerhageAlexander J A GroffenThe 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.http://europepmc.org/articles/PMC5529015?pdf=render |
| spellingShingle | 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 Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains. PLoS ONE |
| title | Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains. |
| title_full | Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains. |
| title_fullStr | Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains. |
| title_full_unstemmed | Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains. |
| title_short | Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains. |
| title_sort | tomosyn associates with secretory vesicles in neurons through its n and c terminal domains |
| url | http://europepmc.org/articles/PMC5529015?pdf=render |
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