Lyn Hitches a Ride on the Golgi

Lyn is a member of the Src family of nonreceptor tyrosine kinases, which are cytosolic proteins that associate with the cytosolic side of the plasma membrane. Kasahara et al. report that Lyn is associated with the Golgi en route to the plasma membrane. At the Golgi, but not the plasma membrane, Lyn colocalized with caveolin. A Lyn mutant lacking the kinase domain was retained in the perinuclear Golgi region. When Lyn and Csk, a kinase that inactivates Lyn by phosphorylating a C-terminal tyrosine and that results in Lyn adopting the "closed" conformation, were both cotransfected, Lyn was retained in the Golgi region. Thus, the open conformation of Lyn appears to contribute to Lyn transport to the plasma membrane. This concept is supported by analysis of mutants in negatively charged residues in the C-lobe, a domain likely exposed when the kinase is in the open conformation. The mutants associated with the Golgi, but their delivery to the plasma membrane was inhibited. Intriguing questions remain: Is the association with the Golgi involved in an endomembrane signaling role for Lyn? Is association with the Golgi a mechanism by which Lyn is regulated? Is association with the Golgi important for the covalent attachment of lipids, such as palmitate, to Lyn? Thus, this Golgi interaction remains an intriguing observation the consequence of which remains to be more fully clarified. K. Kasahara, Y. Nakayama, K. Ikeda, Y. Fukushima, D. Matsuda, S. Horimoto, N. Yamaguchi, Trafficking of Lyn through the Golgi caveolin involves the charged residues on αE and αI helices in the kinase domain. J. Cell Biol. 165 , 641-652 (2004). [Abstract] [Full Text]