Developmental distribution of plasma membrane Ca²⁺‐ATPase isoforms in chick cerebellum

Abstract

The plasma membrane Ca 2؉ -ATPase (PMCA) is highly expressed in the nervous system, but little information is available about its implication in neuronal development. We have analyzed the expression and localization of different isoforms of PMCA in membrane vesicles and sections of chick cerebellum from embryonic day 10 to hatching. We found that the relative amount of each PMCA isoform and their spatiotemporal distribution in the cerebellum are directly linked to precise cellular types during the cerebellar maturation, even in a non-neural tissue as choroid plexus. Purkinje cells contain the highest diversity of PMCA isoforms of the cerebellar cortex since the moment of its morphogenesis. From embryonic day 15, the PMCA2 was highly expressed in the whole Purkinje cell, while PMCAs 1 and 3 had a more restricted distribution in the soma and dendritic branches, and these distributions were evolving according with cell maturation. Other cellular types seem to contain a specific combination of isoforms, but with a well-defined distribution pattern at late moments of development. Thus, PMCAs 1 and 3 were located in the soma of molecular layer interneurons, and only the PMCA2 was observed in granule cells at hatching. Furthermore, PMCA isoforms are also expressed in cellular compartments characterized by a high amount of synapses, suggesting a key role of these proteins in synaptogenesis and in the maturation of neuronal electrophysiological properties.

Molecular interactions of the plasma membrane calcium ATPase 2 at pre- and post-synaptic sites in rat cerebellum

“…Removal of PMCA2 function at both hippocampal and cerebellar synapses also enhances glutamate release (Jensen et al ., 2007) and a form of short term plasticity called paired pulse facilitation as a consequence of elevated residual calcium within the pre-synaptic terminals (Jensen et al ., 2007; Empson et al ., 2007). At the post-synaptic side, PMCA2 is heavily expressed in the dendritic spines of the main output cells of the cerebellum, the Purkinje neurones (Stauffer et al ., 1997; Burette & Weinberg, 2007 Sepúlveda et al ., 2007) where it may be especially suited to controlling local calcium rises within this restricted compartment (Bloodgood & Sabatini, 2007). The location of PMCA isoforms 2b and 4b at synaptic spines is also supported by their molecular interaction with synapse-associated PDZ-domain containing proteins.…”

Compartment‐specific regulation of plasma membrane calcium ATPase type 2 in the chick auditory brainstem

“…The corresponding sequence in the chick PMCA2, TNSDFYSKNQRNEAN, varies from the human sequence only at the last two amino acids. The specificity of the antibody for detecting the chick PMCA2 was tested by western blot analysis in the cerebellum (Sepúlueda et al, 2007) and in the dorsocaudal brainstem in the current study (see below).…”

Contribution of plasma membrane Ca2+ATPase to cerebellar synapse function

“…An initial indication that PMCA2 in the PN dendrites is physiologically important came from our findings that the PN dendrites in the PMCA2 -/-mice are stunted [9] , as if they do not fully develop in the absence of progressively increased expression of PMCA2 that normally takes place during cerebellar development [7,23] (in the rat, Figure 1C).…”