CMT 2D: Cytoplasmic and mitochondrial protein translation in axonal and dendriti

[Guest guest]

Nat Neurosci. 2007 May 27

Cytoplasmic and mitochondrial protein translation in axonal and

dendritic terminal arborization.

Chihara T, Luginbuhl D, Luo L.

[1] Medical Institute, Department of Biological

Sciences, 385 Serra Mall, Stanford University, Stanford, California

94305, USA.

[2] Department of Genetics, Graduate School of Pharmaceutical

Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-

0033, Japan.

We identified a mutation in Aats-gly (also known as gars or glycyl-

tRNA synthetase), the Drosophila melanogaster ortholog of the human

GARS gene that is associated with Charcot-Marie-Tooth neuropathy

type 2D (CMT2D), from a mosaic genetic screen. Loss of gars in

Drosophila neurons preferentially affects the elaboration and

stability of terminal arborization of axons and dendrites. The human

and Drosophila genes each encode both a cytoplasmic and a

mitochondrial isoform.

Using additional mutants that selectively disrupt cytoplasmic or

mitochondrial protein translation, we found that cytoplasmic protein

translation is required for terminal arborization of both dendrites

and axons during development. In contrast, disruption of

mitochondrial protein translation preferentially affects the

maintenance of dendritic arborization in adults.

We also provide evidence that human GARS shows equivalent functions

in Drosophila, and that CMT2D causal mutations show loss-of-function

properties. Our study highlights different demands of protein

translation for the development and maintenance of axons and

dendrites.