TY - JOUR
T1 - Palmitoylation of tetraspanin proteins
T2 - Modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology
AU - Yang, Xiuwei
AU - Claas, Christoph
AU - Kraeft, Stine Kathrein
AU - Chen, Lan Bo
AU - Wang, Zemin
AU - Kreidberg, Jordan A.
AU - Hemler, Martin E.
PY - 2002
Y1 - 2002
N2 - Here we demonstrate that multiple tetraspanin (transmembrane 4 superfamily) proteins are palmitoylated, in either the Golgi or a post-Golgi compartment. Using CD151 as a model tetraspanin, we identified and mutated intracellular N-terminal and C-terminal cysteine palmitoylation sites. Simultaneous mutations of C11, C15, C242, and C243 (each to serine) eliminated >90% of CD151 palmitoylation. Notably, palmitoylation had minimal influence on the density of tetraspanin protein complexes, did not promote tetraspanin localization into detergent-resistant microdomains, and was not required for CID151-α3β1 integrin association. However, the CD151 tetra mutant showed markedly diminished associations with other cell surface proteins, including other transmembrane 4 superfamily proteins (CD9, CD63). Thus, palmitoylation may be critical for assembly of the large network of cell surface tetraspanin-protein interactions, sometimes called the "tetraspanin web." Also, compared with wild-type CD151, the tetra mutant was much more diffusely distributed and showed markedly diminished stability during biosynthesis. Finally, expression of the tetra-CD151 mutant profoundly altered α3 integrin-deficient kidney epithelial cells, such that they converted from a dispersed, elongated morphology to an epithelium-like cobblestone clustering. These results point to novel biochemical and biological functions for tetraspanin palmitoylation.
AB - Here we demonstrate that multiple tetraspanin (transmembrane 4 superfamily) proteins are palmitoylated, in either the Golgi or a post-Golgi compartment. Using CD151 as a model tetraspanin, we identified and mutated intracellular N-terminal and C-terminal cysteine palmitoylation sites. Simultaneous mutations of C11, C15, C242, and C243 (each to serine) eliminated >90% of CD151 palmitoylation. Notably, palmitoylation had minimal influence on the density of tetraspanin protein complexes, did not promote tetraspanin localization into detergent-resistant microdomains, and was not required for CID151-α3β1 integrin association. However, the CD151 tetra mutant showed markedly diminished associations with other cell surface proteins, including other transmembrane 4 superfamily proteins (CD9, CD63). Thus, palmitoylation may be critical for assembly of the large network of cell surface tetraspanin-protein interactions, sometimes called the "tetraspanin web." Also, compared with wild-type CD151, the tetra mutant was much more diffusely distributed and showed markedly diminished stability during biosynthesis. Finally, expression of the tetra-CD151 mutant profoundly altered α3 integrin-deficient kidney epithelial cells, such that they converted from a dispersed, elongated morphology to an epithelium-like cobblestone clustering. These results point to novel biochemical and biological functions for tetraspanin palmitoylation.
UR - http://www.scopus.com/inward/record.url?scp=0036198534&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036198534&partnerID=8YFLogxK
U2 - 10.1091/mbc.01-05-0275
DO - 10.1091/mbc.01-05-0275
M3 - Article
C2 - 11907260
AN - SCOPUS:0036198534
SN - 1059-1524
VL - 13
SP - 767
EP - 781
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 3
ER -