Golgi Distribution of Lyn to Caveolin- and Giantin-Positive <i>cis</i>-Golgi Membranes and the Caveolin-Negative, TGN46-Positive <i>trans</i>-Golgi Network

Abstract

Src-family tyrosine kinases, classified as cytosolic enzymes, have crucial roles in regulating cell proliferation, differentiation, migration and cell-shape changes. Newly synthesized Lyn, a member of Src-family kinases, is biosynthetically accumulated at the cytoplasmic face of caveolin-containing Golgi membranes via posttranslational lipid modifications and then transported to the plasma membrane. However, the precise intra-Golgi localization of Lyn remains elusive. By means of a 19°C block-release technique and short-term brefeldin A treatment, we show here that the distribution of Lyn is not monotonously spread within the Golgi but selectively intensified in two distinct membrane compartments: giantin-and caveolin-positive membranes and trans-Golgi network protein (TGN)46-positive but caveolin-negative membranes. Furthermore, Lyn exits the Golgi from the caveolin-positive cis-Golgi cisternae or the caveolin-negative trans-Golgi network. These results suggest that Lyn moves apart from caveolin, a secretory protein, within the Golgi during Lyn's trafficking to the plasma membrane.

Halting ErbB-2 isoforms retrograde transport to the nucleus as a new theragnostic approach for triple-negative breast cancer

“…While the ability of R2 to block the retrograde trafficking of exogenous toxins and viruses is well acknowledged [ 19 ], its effects on endogenous cargoes remain almost unexplored and limited to specific sets of proteins that function as mediators of protein trafficking. R2 does not affect the trafficking of cation-independent mannose 6-phosphate receptor, which captures mannose 6-phosphate-tagged lysosomal enzymes and is then recycled to the TGN or of TGN protein 46 that mediates protein trafficking between the Golgi and the PM [ 17 , 44 ]. The findings of R2 action on exogenous cargoes and our present discoveries on endogenous ErbB-2 isoforms support the exciting notion that R2 might selectively target cargoes whose localization, via retrotransport, drives either cell death, as toxins and viruses, or neoplastic transformation, such as ErbB-2 when ectopically located in the nucleus.…”

Role of Membrane Cholesterol Levels in Activation of Lyn upon Cell Detachment

“…Intracellular trafficking of Src-family kinases depends on at least three conditions: (1) biosynthetic trafficking; (2) palmitoylation-dependent distribution; and (3) internalization following cell detachment. First, newly synthesized Lyn and c-Yes initially accumulate in the Golgi region, and are then transported to the plasma membrane ( Figure 1 a) [ 11 , 68 , 69 ]. Second, lipid modifications at the N-terminus SH4 domain of Src-family kinases are required to target these kinases to the proper membranes.…”