Emerging Roles of L-Type Voltage-Gated and Other Calcium Channels in T Lymphocytes

In T lymphocytes, calcium ion controls a variety of biological processes including development, survival, proliferation, and effector functions. These distinct and specific roles are regulated by different calcium signals, which are generated by various plasma membrane calcium channels. The repertoire of calcium-conducting proteins in T lymphocytes includes store-operated CRAC channels, transient receptor potential (TRP) channels, P2X channels, and L-type voltage-gated calcium (Cav1) channels. In this paper, we will focus mainly on the role of the Cav1 channels found expressed by T lymphocytes, where these channels appear to operate in a TCR stimulation-dependent and voltage-sensor independent manner. We will review their expression profile at various differentiation stages of CD4 and CD8 T lymphocytes. Then, we will present crucial genetic evidence in favor of a role of these Cav1 channels and related regulatory proteins in both CD4 and CD8 T cell functions such as proliferation, survival, cytokine production and cytolysis. Finally, we will provide evidence and speculate on how these voltage-gated channels might function in the T lymphocyte, a non-excitable cell

Innate recognition of non-self nucleic acids

A variety of innate immune system receptors recognize and respond to the nucleic acids of invading pathogens

The role of CTCF in regulating nuclear organization

The spatial organization of the genome is thought to play an important part in the coordination of gene regulation. New techniques have been used to identify specific long-range interactions between distal DNA sequences, revealing an ever-increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a versatile zinc finger protein with diverse regulatory functions. New data now help define how CTCF mediates both long-range intrachromosomal and interchromosomal interactions, and highlight CTCF as an important factor in determining the three-dimensional structure of the genome

A Nonpolymorphic Class I Gene in the Murine Major Histocompatibility Complex

DNA sequence analysis of a class I gene (QlO), which maps to the Qa2,3 locus in the C57BL/lO (H- 2b haplotype) mouse, reveals that it is almost identical to a cDNA clone (pH16) isolated from a SWR/J (H-2q haplotype) mouse liver cDNA library. Exon 5, in particular, has an unusual structure such that a polypeptide product is unlikely to be anchored in the cell membrane. Our findings suggest that the two sequences are derived from allelic class I genes, which are nonpolymorphic, in contrast to H-2K allelic sequences from the same mice, and they may encode liver-specific polypeptides of unknown function. Our previous studies indicate that the QlO gene is a potential donor gene for the generation of mutations at the H-2K locus by inter-gene transfer of genetic information. Thus the lack of polymorphism in class I genes at the QlO locus implies either that they are not recipients for such exchanges or that selective pressure prevents the accumulation of mutations in genes at this locus

The Inflammasome: First Line of the Immune Response to Cell Stress

The NALP3-inflammasome is a protein complex that stimulates caspase-1 activation to promote the processing and secretion of proinflammatory cytokines. Recent work indicates that the NALP3-inflammasome can be activated by endogenous “danger signals” as well as compounds associated with pathogens (Kanneganti et al., 2006; Mariathasan et al., 2006; Martinon et al., 2006; Sutterwala et al., 2006). Here, we discuss new insights into the regulation of caspase-1 activity in the inflammatory response