RT Journal Article
SR Electronic
T1 Cerebellar Neurodegeneration and Neuronal Circuit Remodeling in Golgi pH Regulator-Deficient Mice
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0427-18.2019
DO 10.1523/ENEURO.0427-18.2019
VO 6
IS 3
A1 Yu-shin Sou
A1 Soichiro Kakuta
A1 Yuji Kamikubo
A1 Kazue Niisato
A1 Takashi Sakurai
A1 Laxmi Kumar Parajuli
A1 Isei Tanida
A1 Hiromitsu Saito
A1 Noboru Suzuki
A1 Kenji Sakimura
A1 Yusuke Maeda
A1 Taroh Kinoshita
A1 Yasuo Uchiyama
A1 Masato Koike
YR 2019
UL http://www.eneuro.org/content/6/3/ENEURO.0427-18.2019.abstract
AB The Golgi apparatus plays an indispensable role in posttranslational modification and transport of proteins to their target destinations. Although it is well established that the Golgi apparatus requires an acidic luminal pH for optimal activity, morphological and functional abnormalities at the neuronal circuit level because of perturbations in Golgi pH are not fully understood. In addition, morphological alteration of the Golgi apparatus is associated with several neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Here, we used anatomical and electrophysiological approaches to characterize morphological and functional abnormalities of neuronal circuits in Golgi pH regulator (GPHR) conditional knock-out mice. Purkinje cells (PCs) from the mutant mice exhibited vesiculation and fragmentation of the Golgi apparatus, followed by axonal degeneration and progressive cell loss. Morphological analysis provided evidence for the disruption of basket cell (BC) terminals around PC soma, and electrophysiological recordings showed selective loss of large amplitude responses, suggesting BC terminal disassembly. In addition, the innervation of mutant PCs was altered such that climbing fiber (CF) terminals abnormally synapsed on the somatic spines of mutant PCs in the mature cerebellum. The combined results describe an essential role for luminal acidification of the Golgi apparatus in maintaining proper neuronal morphology and neuronal circuitry.