A Localized Scaffold for cGMP Increase Is Required for Apical Dendrite Development
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A Localized Scaffold for cGMP Increase Is Required for Apical Dendrite Development. / Szczurkowska, Joanna; Lee, Seong-Il; Guo, Alan; Cwetsch, Andrzej W; Khan, Tanvir; Rao, Sneha; Walz, Gerd; Huber, Tobias B; Cancedda, Laura; Pautot, Sophie; Shelly, Maya.
in: CELL REP, Jahrgang 31, Nr. 2, 14.04.2020, S. 107519.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A Localized Scaffold for cGMP Increase Is Required for Apical Dendrite Development
AU - Szczurkowska, Joanna
AU - Lee, Seong-Il
AU - Guo, Alan
AU - Cwetsch, Andrzej W
AU - Khan, Tanvir
AU - Rao, Sneha
AU - Walz, Gerd
AU - Huber, Tobias B
AU - Cancedda, Laura
AU - Pautot, Sophie
AU - Shelly, Maya
N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2020/4/14
Y1 - 2020/4/14
N2 - Studies in cultured neurons have established that axon specification instructs neuronal polarization and is necessary for dendrite development. However, dendrite formation in vivo occurs when axon formation is prevented. The mechanisms promoting dendrite development remain elusive. We find that apical dendrite development is directed by a localized cyclic guanosine monophosphate (cGMP)-synthesizing complex. We show that the scaffolding protein Scribble associates with cGMP-synthesizing enzymes soluble-guanylate-cyclase (sGC) and neuronal nitric oxide synthase (nNOS). The Scribble scaffold is preferentially localized to and mediates cGMP increase in dendrites. These events are regulated by kinesin KifC2. Knockdown of Scribble, sGC-β1, or KifC2 or disrupting their associations prevents cGMP increase in dendrites and causes severe defects in apical dendrite development. Local cGMP elevation or sGC expression rescues the effects of Scribble knockdown on dendrite development, indicating that Scribble is an upstream regulator of cGMP. During neuronal polarization, dendrite development is directed by the Scribble scaffold that might link extracellular cues to localized cGMP increase.
AB - Studies in cultured neurons have established that axon specification instructs neuronal polarization and is necessary for dendrite development. However, dendrite formation in vivo occurs when axon formation is prevented. The mechanisms promoting dendrite development remain elusive. We find that apical dendrite development is directed by a localized cyclic guanosine monophosphate (cGMP)-synthesizing complex. We show that the scaffolding protein Scribble associates with cGMP-synthesizing enzymes soluble-guanylate-cyclase (sGC) and neuronal nitric oxide synthase (nNOS). The Scribble scaffold is preferentially localized to and mediates cGMP increase in dendrites. These events are regulated by kinesin KifC2. Knockdown of Scribble, sGC-β1, or KifC2 or disrupting their associations prevents cGMP increase in dendrites and causes severe defects in apical dendrite development. Local cGMP elevation or sGC expression rescues the effects of Scribble knockdown on dendrite development, indicating that Scribble is an upstream regulator of cGMP. During neuronal polarization, dendrite development is directed by the Scribble scaffold that might link extracellular cues to localized cGMP increase.
U2 - 10.1016/j.celrep.2020.03.083
DO - 10.1016/j.celrep.2020.03.083
M3 - SCORING: Journal article
C2 - 32294442
VL - 31
SP - 107519
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 2
ER -
