Circadian clocks in mouse and human CD4+ T cells.

Though it has been shown that immunological functions of CD4+ T cells are time of day-dependent, the underlying molecular mechanisms remain largely obscure. To address the question whether T cells themselves harbor a functional clock driving circadian rhythms of immune function, we analyzed clock gene expression by qPCR in unstimulated CD4+ T cells and immune responses of PMA/ionomycin stimulated CD4+ T cells by FACS analysis purified from blood of healthy subjects at different time points throughout the day. Molecular clock as well as immune function was further analyzed in unstimulated T cells which were cultured in serum-free medium with circadian clock reporter systems.

A time to fast, a time to feast: the crosstalk between metabolism and the circadian clock.

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease.

Expression of the atypical protein kinase C (aPKC) isoforms iota/lambda and zeta during mouse embryogenesis.

The atypical C-type protein kinases (aPKCs) comprise the third subclass of the PKC family functionally defined by insensitivity to phorbol esters, diacylgylcerol and calcium. aPKCs have been implicated in numerous biological processes including cell proliferation and survival, cell polarity, migration and inflammation. However, only insufficient data exist with regard to aPKC isoform specificity, since both mammalian aPKCs, PKC iota/lambda and PKC zeta, exhibit a high structural homology and very similar biochemical properties.

Tspy is nonfunctional in the Mongolian gerbil but functional in the Syrian hamster.

The TSPY gene is conserved in placental mammals and encodes the testis-specific protein, Y encoded. Within the testis, TSPY expression is restricted to germ cells, and it is assumed that TSPY plays a role in the proliferation of germ cells. Since it was first discovered in humans, TSPY orthologous gene families have been subsequently characterized in many mammalian lineages.

Control of T helper 2 cell function and allergic airway inflammation by PKCzeta.

Asthma is a disease of chronic airway inflammation in which T helper (Th) 2 cells play a critical role. The molecular mechanisms controlling Th2 differentiation and function are of paramount importance in biology and immunology. PKCzeta has been implicated in the regulation of apoptosis and NF-kappaB, as well as in the control of T-dependent responses, although no defects were detected in naïve T cells from PKCzeta-/- mice.

A unique PDZ ligand in PKCalpha confers induction of cerebellar long-term synaptic depression.

Induction of cerebellar long-term depression (LTD) requires a postsynaptic cascade involving activation of mGluR1 and protein kinase C (PKC). Our understanding of this process has been limited by the fact that PKC is a large family of molecules, many isoforms of which are expressed in the relevant postsynaptic compartment, the cerebellar Purkinje cell. Here, we report that LTD is absent in Purkinje cells in which the alpha isoform of PKC has been reduced by targeted RNA interference or in cells derived from PKCalpha null mice.