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Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance.

Publication ,  Journal Article
Kim, K; Yang, J; Zhong, X-P; Kim, M-H; Kim, YS; Lee, HW; Han, S; Choi, J; Han, K; Seo, J; Prescott, SM; Topham, MK; Bae, YC; Koretzky, G ...
Published in: EMBO J
April 22, 2009

Diacylglycerol (DAG) is an important lipid signalling molecule that exerts an effect on various effector proteins including protein kinase C. A main mechanism for DAG removal is to convert it to phosphatidic acid (PA) by DAG kinases (DGKs). However, it is not well understood how DGKs are targeted to specific subcellular sites and tightly regulates DAG levels. The neuronal synapse is a prominent site of DAG production. Here, we show that DGKzeta is targeted to excitatory synapses through its direct interaction with the postsynaptic PDZ scaffold PSD-95. Overexpression of DGKzeta in cultured neurons increases the number of dendritic spines, which receive the majority of excitatory synaptic inputs, in a manner requiring its catalytic activity and PSD-95 binding. Conversely, DGKzeta knockdown reduces spine density. Mice deficient in DGKzeta expression show reduced spine density and excitatory synaptic transmission. Time-lapse imaging indicates that DGKzeta is required for spine maintenance but not formation. We propose that PSD-95 targets DGKzeta to synaptic DAG-producing receptors to tightly couple synaptic DAG production to its conversion to PA for the maintenance of spine density.

Duke Scholars

Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

April 22, 2009

Volume

28

Issue

8

Start / End Page

1170 / 1179

Location

England

Related Subject Headings

  • Synaptic Transmission
  • Synapses
  • Rats, Sprague-Dawley
  • Rats
  • Protein Kinase C
  • Patch-Clamp Techniques
  • Neurons
  • Mice, Knockout
  • Mice
  • Membrane Proteins
 

Citation

APA
Chicago
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MLA
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Kim, K., Yang, J., Zhong, X.-P., Kim, M.-H., Kim, Y. S., Lee, H. W., … Kim, E. (2009). Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance. EMBO J, 28(8), 1170–1179. https://doi.org/10.1038/emboj.2009.44
Kim, Karam, Jinhee Yang, Xiao-Ping Zhong, Myoung-Hwan Kim, Yun Sook Kim, Hyun Woo Lee, Seungnam Han, et al. “Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance.EMBO J 28, no. 8 (April 22, 2009): 1170–79. https://doi.org/10.1038/emboj.2009.44.
Kim K, Yang J, Zhong X-P, Kim M-H, Kim YS, Lee HW, et al. Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance. EMBO J. 2009 Apr 22;28(8):1170–9.
Kim, Karam, et al. “Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance.EMBO J, vol. 28, no. 8, Apr. 2009, pp. 1170–79. Pubmed, doi:10.1038/emboj.2009.44.
Kim K, Yang J, Zhong X-P, Kim M-H, Kim YS, Lee HW, Han S, Choi J, Han K, Seo J, Prescott SM, Topham MK, Bae YC, Koretzky G, Choi S-Y, Kim E. Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance. EMBO J. 2009 Apr 22;28(8):1170–1179.

Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

April 22, 2009

Volume

28

Issue

8

Start / End Page

1170 / 1179

Location

England

Related Subject Headings

  • Synaptic Transmission
  • Synapses
  • Rats, Sprague-Dawley
  • Rats
  • Protein Kinase C
  • Patch-Clamp Techniques
  • Neurons
  • Mice, Knockout
  • Mice
  • Membrane Proteins