The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure

The postsynaptic density (PSD) is crucial for synaptic functions, but the molecular architecture retaining its structure and components remains elusive. Homer and Shank are among the most abundant scaffolding proteins in the PSD, working synergistically for maturation of dendritic spines. Here, we d...

Full description

Bibliographic Details
Main Authors: Hayashi, Mariko Kato, Tang, Chunyan, Verpelli, Chiara, Narayanan, Radhakrishnan, Stearns, Marissa H., Xu, Rui-Ming, Li, Huilin, Sala, Carlo, Hayashi, Yasunori
Other Authors: Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Format: Article
Language:en_US
Published: Elsevier 2015
Online Access:http://hdl.handle.net/1721.1/96340
_version_ 1811094459467694080
author Hayashi, Mariko Kato
Tang, Chunyan
Verpelli, Chiara
Narayanan, Radhakrishnan
Stearns, Marissa H.
Xu, Rui-Ming
Li, Huilin
Sala, Carlo
Hayashi, Yasunori
author2 Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
author_facet Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Hayashi, Mariko Kato
Tang, Chunyan
Verpelli, Chiara
Narayanan, Radhakrishnan
Stearns, Marissa H.
Xu, Rui-Ming
Li, Huilin
Sala, Carlo
Hayashi, Yasunori
author_sort Hayashi, Mariko Kato
collection MIT
description The postsynaptic density (PSD) is crucial for synaptic functions, but the molecular architecture retaining its structure and components remains elusive. Homer and Shank are among the most abundant scaffolding proteins in the PSD, working synergistically for maturation of dendritic spines. Here, we demonstrate that Homer and Shank, together, form a mesh-like matrix structure. Crystallographic analysis of this region revealed a pair of parallel dimeric coiled coils intercalated in a tail-to-tail fashion to form a tetramer, giving rise to the unique configuration of a pair of N-terminal EVH1 domains at each end of the coiled coil. In neurons, the tetramerization is required for structural integrity of the dendritic spines and recruitment of proteins to synapses. We propose that the Homer-Shank complex serves as a structural framework and as an assembly platform for other PSD proteins.
first_indexed 2024-09-23T16:00:25Z
format Article
id mit-1721.1/96340
institution Massachusetts Institute of Technology
language en_US
last_indexed 2024-09-23T16:00:25Z
publishDate 2015
publisher Elsevier
record_format dspace
spelling mit-1721.1/963402022-10-02T05:40:42Z The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure Hayashi, Mariko Kato Tang, Chunyan Verpelli, Chiara Narayanan, Radhakrishnan Stearns, Marissa H. Xu, Rui-Ming Li, Huilin Sala, Carlo Hayashi, Yasunori Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory RIKEN-MIT Center for Neural Circuit Genetics Hayashi, Mariko Kato Hayashi, Yasunori Stearns, Marissa H. Narayanan, Radhakrishnan The postsynaptic density (PSD) is crucial for synaptic functions, but the molecular architecture retaining its structure and components remains elusive. Homer and Shank are among the most abundant scaffolding proteins in the PSD, working synergistically for maturation of dendritic spines. Here, we demonstrate that Homer and Shank, together, form a mesh-like matrix structure. Crystallographic analysis of this region revealed a pair of parallel dimeric coiled coils intercalated in a tail-to-tail fashion to form a tetramer, giving rise to the unique configuration of a pair of N-terminal EVH1 domains at each end of the coiled coil. In neurons, the tetramerization is required for structural integrity of the dendritic spines and recruitment of proteins to synapses. We propose that the Homer-Shank complex serves as a structural framework and as an assembly platform for other PSD proteins. Massachusetts Institute of Technology. Biophysical Instrumentation Facility RIKEN Brain Science Institute National Institutes of Health (U.S.) (Grant R01DA17310) Japan. Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research) 2015-04-02T17:28:12Z 2015-04-02T17:28:12Z 2009-04 2008-11 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/96340 Hayashi, Mariko Kato, Chunyan Tang, Chiara Verpelli, Radhakrishnan Narayanan, Marissa H. Stearns, Rui-Ming Xu, Huilin Li, Carlo Sala, and Yasunori Hayashi. “The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure.” Cell 137, no. 1 (April 2009): 159–171. © 2009 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.cell.2009.01.050 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier
spellingShingle Hayashi, Mariko Kato
Tang, Chunyan
Verpelli, Chiara
Narayanan, Radhakrishnan
Stearns, Marissa H.
Xu, Rui-Ming
Li, Huilin
Sala, Carlo
Hayashi, Yasunori
The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure
title The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure
title_full The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure
title_fullStr The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure
title_full_unstemmed The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure
title_short The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure
title_sort postsynaptic density proteins homer and shank form a polymeric network structure
url http://hdl.handle.net/1721.1/96340
work_keys_str_mv AT hayashimarikokato thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT tangchunyan thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT verpellichiara thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT narayananradhakrishnan thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT stearnsmarissah thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT xuruiming thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT lihuilin thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT salacarlo thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT hayashiyasunori thepostsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT hayashimarikokato postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT tangchunyan postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT verpellichiara postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT narayananradhakrishnan postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT stearnsmarissah postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT xuruiming postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT lihuilin postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT salacarlo postsynapticdensityproteinshomerandshankformapolymericnetworkstructure
AT hayashiyasunori postsynapticdensityproteinshomerandshankformapolymericnetworkstructure