Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane

B cell linker protein (BLNK) and Src homology 2 domain-containing leukocyte protein of 76 kD (SLP-76) are adaptor proteins required for B cell recepto r (BCR) and T cell receptor function, respectively. Here, we show that expr ession of SLP-76 cannot reconstitute BCR function in Zap-70(+)BLNK(-) B cel ls. This could be attributable to inability of SLP-76 to be recruited into glycolipid-enriched microdomains (GEMs) after antigen receptor cross-linkin g. Supporting this idea, the BCR function was restored when a membrane-asso ciated SLP-76 chimera was enforcedly localized to GE:Ms. Moreover, we demon strate that addition of both linker for activation of T cells (LAT) and Grb 2-related adaptor downstream of Shc (Gads) to SLP-76 allow SLP-76 to be rec ruited into GEMs, whereby the BCR function is reconstituted. The Gads funct ion was able to be replaced by overexpression of Grb2. In contrast to SLP-7 6, BLNK did not require Grb2 families for its recruitment to GEMs. Hence, t hese data suggest a functional overlap between BLNK and SLP-76, while empha sizing the difference in requirement for additional adaptor molecules in th eir targeting to GEMs.