T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels.

The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) α1S subunits during calcium entry after TCR stimulation.

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 channels, P2X channels, and L-type voltage-gated calcium (Cav1) channels.

Myocardial mitochondrial injury induced by pulmonary exposure to particulate matter in rats.

Exposure to air pollution has been associated with acute myocardial ischemia, impaired myocardrial function, and ST-segment depression. Particulate matter (PM)-associated metals, especially vanadium and nickel, have been implicated in observed cardiovascular impairments. We aimed to assess the effect of single intratracheal pulmonary exposure to vanadium-rich respirable oil combustion PM (HP-10) on the intrinsic myocardial ischemic tolerance and mitochondrial integrity in rats.

Roles of Ca(v) channels and AHNAK1 in T cells: the beauty and the beast.

T lymphocytes require Ca2+ entry though the plasma membrane for their activation and function. Recently, several routes for Ca2+ entry through the T-cell plasma membrane after activation have been described. These include calcium release-activated channels (CRAC), transient receptor potential (TRP) channels, and inositol-1,4,5-trisphosphate receptors (IP3Rs).

Requirement for AHNAK1-mediated calcium signaling during T lymphocyte cytolysis.

Cytolytic CD8(+) T cells (CTLs) kill virally infected cells, tumor cells, or other potentially autoreactive T cells in a calcium-dependent manner. To date, the molecular mechanism that leads to calcium intake during CTL differentiation and function has remained unresolved. We demonstrate that desmoyokin (AHNAK1) is expressed in mature CTLs, but not in naive CD8(+) T cells, and is critical for calcium entry required for their proper function during immune response.

A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation.

Engagement of the T cell antigen receptor (TCR) during antigen presentation initiates a coordinated action of a large number of signaling proteins and ion channels. AHNAK1 is a scaffold protein, highly expressed by CD4+ T cells, and is a critical component for calcium signaling. We showed that AHNAK1-deficient mice were highly susceptible to Leishmania major infection.

Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function.

Calcium ion is a universal signaling intermediate, which is known to control various biological processes. In excitable cells, voltage-gated calcium channels (Cav) are the major route of calcium entry and regulate multiple functions such as contraction, neurotransmitter release, and gene transcription. Here we show that T lymphocytes, which are nonexcitable cells, express both regulatory beta and pore-forming Cav1 alpha1 subunits of Cav channels, and we provide genetic evidence for a critical role of the Cav beta3 and Cav beta4 regulatory subunits in T lymphocyte function.

Requirement of voltage-gated calcium channel beta4 subunit for T lymphocyte functions.

Calcium is known to play vital roles in diverse physiological processes, and it is known that voltage-gated calcium channels (Cav) mediate calcium influx in excitable cells. However, no consensus exists on the molecular identity of the calcium channels present in nonexcitable cells such as T lymphocytes. Here, we demonstrate that T lymphocytes express both regulatory beta4 and poreforming Cav1 alpha1 subunits of Cav channels.

Invariant chain-induced B cell differentiation requires intramembrane proteolytic release of the cytosolic domain.

Immature B cells differentiate in the spleen into mature B cells, a process that is essential for their participation in the immune response. Previously, we showed that the MHC class II chaperone, invariant chain (Ii), controls this differentiation to the mature stage. Ii cytosolic domain-induced B cell maturation involves activation of transcription mediated by the NF-kappaB p65/RelA homodimer and requires the B cell enriched coactivator, TAF(II)105.

Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity.

Early stages of B cell development take place in the bone marrow, resulting in formation of immature B cells, which migrate to the spleen for their final differentiation into mature cells. This final maturation step is essential for B cells to become responsive to antigens and to participate in the immune response. Previously, we showed that the MHC class II chaperone, invariant chain (Ii), controls the differentiation of B cells from the immature to the mature stage.