A MyD88 meddles with survival

In the MyD88 family of cytosolic adaptor proteins, the newest member is the group's black sheep, according to Kim et al. (page 2063). Whereas most MyD88 proteins turn on antipathogen responses within myeloid cells, the rebel, MyD88-5, instigates cell death within neurons.

MyD88-1–4 all respond to Toll-like receptor (TLR) activation in leukocytes and stimulate innate immune responses. MyD88-5, however, does not transmit TLR signals or induce innate response genes. Two extra domains in MyD88-5 that may allow it to interact with cytoskeletal proteins hint at an entirely different function.

Kim et al. now find that the protein is not even expressed in most leukocytes and instead is found mainly in neurons. There, MyD88-5 bound to microtubules and studded the outer membranes of mitochondria. Mitochondria formed clusters when MyD88-5 expression levels were...