Cathepsin L coexists with Cytotoxic T-lymphocyte Antigen-2 alpha in distinct regions of the mouse brain

Abstract

Cathepsins B and L are two prominent members of cystein proteases with broad substrate specificity and are known to be involved in the process of intra- and extra-cellular protein degradation and turnover. The propeptide region of cathepsin L is identical to Cytotoxic T-lymphocyte antigen-2α (CTLA-2α) discovered in mouse activated T-cells and mast cells. CTLA-2α exhibits selective inhibitory activities against papain and cathepsin L. We previously demonstrated the distribution pattern of the CTLA-2α protein in mouse brain by immunohistochemistry, describing that it is preferentially localized within nerve fibre bundles than neuronal cell bodies. In the present study we report colocalization of cathepsin L and CTLA-2α by double labeling immunofluorescence analysis in the mouse brain. In the telencephalon, immunoreactivity was identified in cerebral cortex and subcortical structures, hippocampus and amygdala. Within the diencephalon intense colocalization was detected in stria medullaris of thalamus, mammillothalamic tract, medial habenular nucleus and choroid plexus. Colocalization signals in the mesencephalon were strong in the hypothalamus within supramammillary nucleus and lateroanterior hypothalamic nucleus while in the cerebellum was in the deep white matter, granule cell layer and Purkinje neurons but moderately in stellate, and basket cells of cerebellar cortex. The distribution pattern indicates that the fine equilibrium between synthesis and secretion of cathespin L and CTLA-2α is part of the brain processes to maintain normal growth and development. The functional implication of cathespin L coexistence with CTLA-2α in relation to learning, memory and disease mechanisms is discussed.