Distribution of calcium-binding proteins in the cerebellum

Abstract

Calcium plays a fundamental role in the cell as second messenger and is principally regulated by calcium-binding proteins. Although these proteins share in common their ability to bind calcium, they belong to different subfamilies. They present, in general, specific developmental and distribution patterns. Most Purkinje cells express the fast and slow calcium buffer proteins calbindin-D28k and parvalbumin, whereas basket, stellate and Golgi cells the slow buffer parvalbumin only. They are, almost all, calretinin negative. Granule, Lugaro and unipolar brush cells present an opposite immunoreactivity profile, most of them being calretinin positive while lacking calbindin-D28k and parvalbumin. The developmental pattern of appearance of these proteins seems to follow the maturation of neurons. Calbindin-D28k appears early, shortly after cessation of mitosis when neurons become ready to start migration and differentiation while parvalbumin is expressed later in parallel with an increase in neuronal activity. The other proteins are generally detected later. During development, some of these proteins, like calretinin, are transiently expressed in specific cellular subpopulations. The function of these proteins is not fully understood, although strong evidence supports a prominent role in physiological settings with altered calcium concentrations. These proteins regulate and are regulated by intracellular calcium level. For example, they may directly or indirectly enable sensitization or desensitization of calcium channels, and may further block calcium entry into the cells, like the calcium-sensor proteins, that have been shown to be potent and specific modulators of ion channels, which may allow for feedback control of current function and hence signaling. The absence of calcium buffer proteins results in marked abnormalities in cell firing; with alterations in simple and complex spikes or transformation of depressing synapses into facilitating synapses. Calcium-binding protein implication in resistance to degeneration is still a controversial issue. Neurons rich in calcium-binding proteins, especially calbindin-D28k and parvalbumin, seem to be relatively resistant to degeneration in a variety of acute and chronic disorders. However other data support that an absence of calcium-binding proteins may also have a neuroprotective effect. It is not unlikely that neurons may face a dual action mechanism where a decrease in calcium-binding proteins has a first short-term beneficial effect while it becomes detrimental for the cell over the long term.

Different Types of Cerebellar GABAergic Interneurons Originate from a Common Pool of Multipotent Progenitor Cells

“…Their phenotypes were determined on the basis of several criteria, including (1) morphological features, (2) expression of type-specific markers, (3) morphometric parameters (e.g., cell body size), and (4) position in the host cortical layers or deep nuclei. The different types of GABAergic interneurons were identified according to the expression pattern of a set of distinctive markers and assigned to different categories: deep nuclei interneurons [NeuN/calretinin (Bastianelli, 2003;Weyer and Schilling, 2003)]; granular layer interneurons for Golgi [mGluR2/Pax-2 Grimaldi and Rossi, 2006)] and Lugaro cells [calretinin (Dino et al, 1999;Bastianelli, 2003)]; and molecular layer interneurons for basket and stellate cells [parvalbumin (Celio, 1990)]. Except for rare elements ectopically positioned in the white matter (see below and Fig.…”

“…2 A, 3A, B) (Jankovski et al, 1996), whereas the latter stains smaller ovoid-shaped cells (Figs. 2 A, 3 E, F ) (Bastianelli, 2003). Hoshino et al (2005) reported that the SMI32-positive cells do not colabel with anti-GABA antibodies and represent the large glutamatergic projection neurons.…”

Optimized Immunohistochemical Analysis of Cerebellar Purkinje Cells Using a Specific Biomarker, Calbindin D28k

“…Calbindin D28k (CaB), a member of calcium-binding protein superfamily, is a PCspecific protein in the cerebellum (Bastianelli, 2003). CaB has six EF-hand motifs, serves as a cytosolic calcium buffer, and plays an important role in motor functions (Schwaller et al, 2002;Simons and Pellionisz, 2006;Whitney et al, 2008b).…”

Different protein profiles in inferior colliculus and cerebellum: A comparative proteomic study

“…These closely related cytosolic proteins bind free Ca 2ϩ -ions and thus contribute to the fast Ca 2ϩ -buffer capacity of cells. Strong expression of calbindin in cerebellar Purkinje cells was demonstrated by immunohistochemistry (Celio, 1990;Fortin et al, 1998;Bastianelli, 2003), whereas granule cells express calretinin (Resibois and Rogers, 1992;Marini et al, 1997;Bearzatto et al, 2005). In contrast, only a faint expression of calbindin was shown in the IC (Celio, 1990;Friauf, 1994;Tardif et al, 2003).…”