Serotonin-induced regulation of the actin network for learning-related synaptic growth requires Cdc42, N-WASP, and PAK in Aplysia sensory neurons.

Abstract:

:Application of Clostridium difficile toxin B, an inhibitor of the Rho family of GTPases, at the Aplysia sensory to motor neuron synapse blocks long-term facilitation and the associated growth of new sensory neuron varicosities induced by repeated pulses of serotonin (5-HT). We have isolated cDNAs encoding Aplysia Rho, Rac, and Cdc42 and found that Rho and Rac had no effect but that overexpression in sensory neurons of a dominant-negative mutant of ApCdc42 or the CRIB domains of its downstream effectors PAK and N-WASP selectively reduces the long-term changes in synaptic strength and structure. FRET analysis indicates that 5-HT activates ApCdc42 in a subset of varicosities contacting the postsynaptic motor neuron and that this activation is dependent on the PI3K and PLC signaling pathways. The 5-HT-induced activation of ApCdc42 initiates reorganization of the presynaptic actin network leading to the outgrowth of filopodia, some of which are morphological precursors for the learning-related formation of new sensory neuron varicosities.

journal_name

Neuron

journal_title

Neuron

authors

Udo H,Jin I,Kim JH,Li HL,Youn T,Hawkins RD,Kandel ER,Bailey CH

doi

10.1016/j.neuron.2005.01.044

subject

Has Abstract

pub_date

2005-03-24 00:00:00

pages

887-901

issue

6

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(05)00113-3

journal_volume

45

pub_type

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