cGMP-Dependent Protein Kinase Encoded by foraging Regulates Motor Axon Guidance in Drosophila by Suppressing Lola Function.
Correct pathfinding and target recognition of a developing axon are exquisitely regulated processes that require multiple guidance factors. Among these factors, the second messengers, cAMP and cGMP, are known to be involved in establishing the guidance cues for axon growth through different intracellular signaling pathways. However, whether and how cGMP-dependent protein kinase (PKG) regulates axon guidance remains poorly understood. Here, we show that the motor axons of intersegmental nerve b (ISNb) in the Drosophila embryo display targeting defects during axon development in the absence of foraging(for), a gene encoding PKG.In vivo tag expression revealed PKG to be present in the ventral nerve code at late embryonic stages, supporting its function in embryonic axon guidance. Mechanistic studies showed that the transcription factor longitudinal lacking(lola) genetically interacts with for.PKG physically associates with the LolaT isoform via the C-terminal zinc-finger-containing domain. Overexpression of PKG leads to the cytoplasmic retention of LolaT in S2 cells, suggesting a role for PKG in mediating the nucleocytoplasmic trafficking of Lola. Together, these findings reveal a novel function of PKG in regulating the establishment of neuronal connectivity by sequestering Lola in the cytoplasm.


CONCLUSIONS
Axon pathfinding and target recognition are important processes in the formation of specific neuronal connectivity, which rely upon precise coordinated deployment of multiple guidance factors. This paper reveals the role of cGMP-dependent protein kinase (PKG) in regulating the pathfinding and targeting of the developing axons in Drosophila Moreover, our study indicates that PKG regulates the cytoplasmic-nuclear trafficking of the transcription factor LolaT, suggesting a mechanism of PKG in directing motor axon guidance. These findings highlight a new function of PKG in axon guidance by suppressing a transcription factor.
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, University of the Chinese Academy of Sciences, Beijing 100039, China, and.
Qionglin
Q
Peng
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, University of the Chinese Academy of Sciences, Beijing 100039, China, and.
Yijin
Y
Wang
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Meixia
M
Li
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, University of the Chinese Academy of Sciences, Beijing 100039, China, and.
Deliang
D
Yuan
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Mengbo
http://orcid.org/0000-0002-9037-0974
M
Xu
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Changqing
C
Li
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Zhefeng
Z
Gong
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, rjiao@sun5.ibp.ac.cn liuli@sun5.ibp.ac.cn.
Renjie
R
Jiao
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, University of the Chinese Academy of Sciences, Beijing 100039, China, and Key Laboratory of Mental Health, Chinese Academy of Sciences, Beijing 100101, China rjiao@sun5.ibp.ac.cn liuli@sun5.ibp.ac.cn.
Li
L
Liu
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D021381:Protein Transport / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D014157:Transcription Factors; C121765:lola protein, Drosophila; D017869:Cyclic GMP-Dependent Protein Kinases; C528566:for protein, Drosophila
Drosophila; Lola; PKG; motor axon guidance