http://www.sciencedirect.com/science/article/pii/S0143416012001583
Abstract
Changes
in PMCA2 and PMCA3 expression during neuronal development are tightly
linked to structural and functional modifications in Ca2+
handling machinery. Using antisense strategy we obtained stably
transfected PC12 lines with reduced level of PMCA2 or PMCA3, which were
then subjected to dibutyryl-cAMP differentiation. Reduced level of
neuron-specific PMCAs led to acceleration of differentiation and
formation of longer neurites than in control PC12 line. Treatment with
dibutyryl-cAMP was associated with retraction of growth cones and
intensified formation of varicosities. In PMCA2-reduced cells
development of apoptosis and DNA laddering were detected. Higher amounts
of constitutive isoforms PMCA1 and PMCA4, their putative extended
location to gaps left after partial removal of PMCA2 or PMCA3, together
with increased SERCA may indicate the induction of compensatory
mechanism in modified cells. Functional studies showed altered
expression of certain types of VDCCs in PMCA-reduced cells, which
correlated with their higher contribution to Ca2+ influx. The
cell response to PMCAs suppression suggests the interplay between
transcription level of two opposite calcium-transporting systems i.e.
voltage- and store depletion-activated channels facilitating Ca2+ influx and calcium pumps responsible for Ca2+ clearance, as well highlights the role of both neuron-specific PMCA isoforms in the control of PC12 cells differentiation.
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