Fig. 8

Pleiotropic functions of Htt in the TLR-4 signal transduction system in BMMCs. Upon LPS stimulus, TLR-4 is translocated to the perinuclear area in Htt-containing vesicles by a mechanism depending on the activity of dynamin. This process leads to the activation of the ERK1/2-ELK-1 signaling pathway, which is involved in the accumulation of c-fos and TNF mRNAs, along with the secretion of TNF via TACE activation. The expression of mHtt in BMMCs not only impairs the ERK1/2 signaling cascade, but also decreases IKK phosphorylation, which has been associated with the phosphorylation of SNAP23 and TNF secretion upon TLR-4 triggering in this cell type. Anaphylactic degranulation triggered by FcεRI seems to be independent on the function of Htt