Golli, a New Mechanism for Regulating T Cell Activation

Abstract

Golli proteins, which are generated by alternative splicing from the gene that encodes myelin basic proteins (which are found only in the nervous system), are expressed not only in the nervous system but also in immune tissues. Feng et al. , who previously showed that golli negatively regulates T cell activation, uncovered a hitherto undescribed mechanism for this involving inhibition of calcium influx. When stimulated with antibody directed against CD3 (anti-CD3) or with anti-CD3 plus anti-CD28, golli-deficient T cells proliferated more than did wild-type cells; consistent with this, golli-deficient cells stimulated with anti-CD3 plus anti-CD20 produced more interleukin-2 than did wild-type cells. No differences in extracellular signal-regulated kinase (ERK) or c-Jun N-terminal kinase (JNK) activation were apparent between golli-deficient and wild-type T cells in response to anti-CD3 stimulation; however, the increase in intracellular calcium was enhanced. Calcium imaging in the presence or absence of extracellular calcium, thapsigargin, or both suggested that golli inhibited calcium influx through store-operated calcium channels. Moreover, patch-clamp analysis of golli-deficient cells revealed increased inward calcium current in response to store depletion. A portion of T cell golli protein was associated with the plasma membrane, and experiments in which cells were transfected with either wild-type golli protein or a myristoylation mutant indicated that membrane association was required for golli's inhibition of calcium influx. Thus, the authors conclude that golli acts as a negative regulator of T cell activation through a mechanism completely distinct from that of other negative regulators of T cell receptor signaling. J.-M. Feng, Y. K. Hu, L.-H. Xie, C. S. Colwell, X. M. Shao, X.-P. Sun, B. Chen, H. Tang, A. T. Campagnoni, Golli protein negatively regulates store depletion-induced calcium influx in T cells. Immunity 24 , 717-727 (2006). [PubMed]