Isoform‐specific distribution of the plasma membrane Ca²⁺ ATPase in the rat brain

Abstract

Regulation of cytoplasmic calcium is crucial both for proper neuronal function and cell survival. The concentration of Ca2+ in cytoplasm of a neuron at rest is 10,000 times lower than in the extracellular space, pointing to the importance of the transporters that extrude intracellular Ca2+. The family of plasma membrane calcium-dependent ATPases (PMCAs) represent a major component of the Ca2+ regulatory system. However, little information is available on the regional and cellular distribution of these calcium pumps. We used immunohistochemistry to investigate the distribution of each of the four PMCA isoforms (PMCA1-4) in the rat brain. Each isoform exhibited a remarkably precise and distinct pattern of distribution. In many cases, PMCA isoforms in a single brain structure were differentially expressed within different classes of neurons, and within different subcellular compartments. These data show that each isoform is independently organized and suggest that PMCAs may play a more complex role in calcium homeostasis than generally recognized.

Plasma Membrane Ca2+ATPase 2 Contributes to Short-Term Synapse Plasticity at the Parallel Fiber to Purkinje Neuron Synapse

“…The rich expression of PMCA2 within PNs and their dendritic spines (Burette et al, 2003) raises the possibility that postsynaptic Ca 2ϩ homeostasis and downstream signaling may be impaired in the absence of PMCA2. Indeed, the slower PMCA2 "b" splice variant interacts with the postsynaptic density protein 95 in vitro (DeMarco and Strehler, 2001) and, previously, PMCA activity has been shown to influence Ca 2ϩ dynamics in hippocampal spines (Scheuss et al, 2006).…”

“…PMCAs 2 and 3 are enriched within excitable cells where their faster activation and extrusion rates, compared with the more ubiquitously expressed PMCA isoforms 1 and 4 (Brini et al, 2003), are ideally suited to control fast [Ca 2ϩ ] i dynamics. This is particularly true in the cerebellum where the predominant PMCA isoforms 2 and 3 are expressed throughout the molecular (ML) and granule cell (GC) layers (Burette et al, 2003). Furthermore, the importance of PMCA2 for cerebellar function is indicated from studies on the PMCA2 knock-out mouse.…”

The Homer-1 protein Ania-3 interacts with the plasma membrane calcium pump

“…PMCA2b is also abundant in the brain and present in the soma and dendrites of hippocampal pyramidal neurons [23,28,29]. To confirm the co-expression of endogenous Homer 1/Ania-3 and PMCA2b, we double-labeled mature (2 to 3 week-old) rat hippocampal neurons with antibodies specific for Homer and PMCA2.…”

Ontogeny of plasma membrane Ca2+ ATPase isoforms in the neural retina of the postnatal rat

“…The plasma membrane Ca 2ϩ ATPases~PM-CAs! are an important Ca 2ϩ clearance system found in all neurons that extrude Ca 2ϩ across the plasma membrane~Hammes et Stauffer et al, 1995;Filoteo et al, 1997;Zacharias & Kappen, 1999;Burette et al, 2003;reviewed in Strehler & Zacharias, 2001;Strehler & Treiman, 2004!. PMCAs play a key role in Ca 2ϩ signaling of sensory tissues, such as the cochlea~Furuta et al., 1998;Boyer et al, 2001;Dumont et al, 2001!…”

“…The different PMCA isoforms are expressed in a cell typespecific manner in the adult mouse retina, rat cochlea, and rat brain Dumont et al, 2001;Burette et al, 2003!. Only a few studies have documented the specific cellular pattern of expression of the different PMCA isoforms in developing brain tissues~Brandt & Neve, 1992;Furuta et al, 1998;Kozel et al, 1998;Zacharias & Kappen, 1999!. None have described this for the developing mammalian retina.…”