Loss of Drosophila melanogaster p21-activated kinase 3 suppresses defects in synapse structure and function caused by spastin mutations.

Abstract:

:Microtubules are dynamic structures that must elongate, disassemble, and be cleaved into smaller pieces for proper neuronal development and function. The AAA ATPase Spastin severs microtubules along their lengths and is thought to regulate the balance between long, stable filaments and shorter fragments that seed extension or are transported. In both Drosophila and humans, loss of Spastin function results in reduction of synaptic connections and disabling motor defects. To gain insight into how spastin is regulated, we screened the Drosophila melanogaster genome for deletions that modify a spastin overexpression phenotype, eye size reduction. One suppressor region deleted p21-activated kinase 3 (pak3), which encodes a member of the Pak family of actin-regulatory enzymes, but whose in vivo function is unknown. We show that pak3 mutants have only mild synaptic defects at the larval neuromuscular junction, but exhibit a potent genetic interaction with spastin mutations. Aberrant bouton morphology, microtubule distribution, and synaptic transmission caused by spastin loss of function are all restored to wild type when pak3 is simultaneously reduced. Neuronal overexpression of pak3 induces actin-rich thin projections, suggesting that it functions in vivo to promote filopodia during presynaptic terminal arborization. pak3 therefore regulates synapse development in vivo, and when mutated, suppresses the synaptic defects that result from spastin loss.

journal_name

Genetics

journal_title

Genetics

authors

Ozdowski EF,Gayle S,Bao H,Zhang B,Sherwood NT

doi

10.1534/genetics.111.130831

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

123-35

issue

1

eissn

0016-6731

issn

1943-2631

pii

genetics.111.130831

journal_volume

189

pub_type

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