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In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation.

Publication ,  Journal Article
Spence, EF; Dube, S; Uezu, A; Locke, M; Soderblom, EJ; Soderling, SH
Published in: Nat Commun
January 23, 2019

Excitatory synapse formation during development involves the complex orchestration of both structural and functional alterations at the postsynapse. However, the molecular mechanisms that underlie excitatory synaptogenesis are only partially resolved, in part because the internal machinery of developing synapses is largely unknown. To address this, we apply a chemicogenetic approach, in vivo biotin identification (iBioID), to discover aspects of the proteome of nascent synapses. This approach uncovered sixty proteins, including a previously uncharacterized protein, CARMIL3, which interacts in vivo with the synaptic cytoskeletal regulator proteins SrGAP3 (or WRP) and actin capping protein. Using new CRISPR-based approaches, we validate that endogenous CARMIL3 is localized to developing synapses where it facilitates the recruitment of capping protein and is required for spine structural maturation and AMPAR recruitment associated with synapse unsilencing. Together these proteomic and functional studies reveal a previously unknown mechanism important for excitatory synapse development in the developing perinatal brain.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 23, 2019

Volume

10

Issue

1

Start / End Page

386

Location

England

Related Subject Headings

  • Synapses
  • Proteomics
  • Proteome
  • Neurons
  • Neurogenesis
  • Microtubules
  • Microfilament Proteins
  • Mice, Inbred C57BL
  • Humans
  • HEK293 Cells
 

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Spence, E. F., Dube, S., Uezu, A., Locke, M., Soderblom, E. J., & Soderling, S. H. (2019). In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation. Nat Commun, 10(1), 386. https://doi.org/10.1038/s41467-019-08288-w
Spence, Erin F., Shataakshi Dube, Akiyoshi Uezu, Margaret Locke, Erik J. Soderblom, and Scott H. Soderling. “In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation.Nat Commun 10, no. 1 (January 23, 2019): 386. https://doi.org/10.1038/s41467-019-08288-w.
Spence EF, Dube S, Uezu A, Locke M, Soderblom EJ, Soderling SH. In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation. Nat Commun. 2019 Jan 23;10(1):386.
Spence, Erin F., et al. “In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation.Nat Commun, vol. 10, no. 1, Jan. 2019, p. 386. Pubmed, doi:10.1038/s41467-019-08288-w.
Spence EF, Dube S, Uezu A, Locke M, Soderblom EJ, Soderling SH. In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation. Nat Commun. 2019 Jan 23;10(1):386.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 23, 2019

Volume

10

Issue

1

Start / End Page

386

Location

England

Related Subject Headings

  • Synapses
  • Proteomics
  • Proteome
  • Neurons
  • Neurogenesis
  • Microtubules
  • Microfilament Proteins
  • Mice, Inbred C57BL
  • Humans
  • HEK293 Cells