FIG4, Charcot‐Marie‐Tooth disease, and hypopigmentation: a role for phosphoinositides in melanosome biogenesis?

Abstract

Pigmentation defects in mice and humans result from mutations in any of over 120 genes, many of which also influence additional physiological functions (Bennett and Lamoreux, 2003). Identification of genes mutated in diseases such as Hermansky-Pudlak and Chediak-Higashi syndromes and their corresponding mouse models have unveiled components of the intracellular trafficking machinery required for the formation of melanosomes and other tissue-specific lysosome-related organelles (Raposo et al., 2007). In a recent report, Chow and colleagues (Chow et al., 2007) identify another likely component of this machinery by mapping the gene that is defective in both the “pale tremor” mouse and a form of Charcot-Marie-Tooth (CMT) disease in humans. The gene, Fig4 (in the mouse; FIG4 in humans), encodes an inositol phospholipid phosphatase that likely regulates the biogenesis of melanosomes and neurosecretory granules. Its identification provides a new twist that will likely enhance our emerging understanding of melanosome protein trafficking.