Functional and immunocytochemical evidence for the expression and localization of the secretory pathway Ca²⁺‐ATPase isoform 1 (SPCA1) in cerebellum relative to other Ca²⁺ pumps

Abstract

Membrane fractions of pig cerebellum show Ca 2+ -ATPase activity and Ca 2+ transport due to the presence of the secretory pathway Ca 2+-ATPase (SPCA). The SPCA1 isoform shows a wide distribution in the neurons of pig cerebellum, where it is found in the Golgi complex of the soma of Purkinje, stellate, basket and granule cells, and also in more distal components of the secretory pathway associated with a synaptic localization such as in cerebellar glomeruli. The SPCA1 may be involved in loading the Golgi complex and the secretory vesicles of these specific neuronal cell types with Ca ) levels as well as the local cytosolic Ca 2+ levels. In addition, it helps to specify the zones that are most vulnerable to Ca 2+ and/or Mn 2+ dyshomeostasis, a condition that is held responsible of an increasing number of neurological disorders.

The Ca2+ Pumps of the Endoplasmic Reticulum and Golgi Apparatus

“…SPCA1 was localized in Golgi stacks of the soma and the initial part of the primary dendritic trunk in main cortical, hippocampal and cerebellar neurons, and is present from the earliest postnatal stages onward. Although SPCA1 expression has been reported in different glial cultures (Murin et al 2006), other efforts to show SPCA-or SERCA-pump expression in glial cells in nervous tissue were unsuccessful (Baba-Aissa et al 1996b;Sepulveda et al 2007;Sepulveda et al 2008). Because glial cells express high levels of the Mn 2þ -dependent glutamine synthetase (Wedler and Denman 1984), the low levels of SPCAs argues against a role of SPCAs in Mn 2þ uptake.…”

Silencing the SPCA1 (Secretory Pathway Ca2+-ATPase Isoform 1) Impairs Ca2+Homeostasis in the Golgi and Disturbs Neural Polarity

“…The secretory pathway Ca 2ϩ -ATPases (SPCA1, 2) are found in the membranes of the Golgi apparatus and constitute the most recently identified P-type Ca 2ϩ pumps in neural tissue, where SPCA1 is the major isoform (Wootton et al, 2004;Vanoevelen et al, 2005;Xiang et al, 2005;Murin et al, 2006;Sepú lveda et al, 2007). Together with Ca 2ϩ -ATPases of the plasma membrane (PMCA) and of the sarco(endo)plasmic reticulum (SERCA), SPCAs are active participants in neural Ca 2ϩ homeostasis (Wootton et al, 2004;Mata and Sepú lveda, 2005;Sepú lveda et al, 2007).…”

“…Together with Ca 2ϩ -ATPases of the plasma membrane (PMCA) and of the sarco(endo)plasmic reticulum (SERCA), SPCAs are active participants in neural Ca 2ϩ homeostasis (Wootton et al, 2004;Mata and Sepú lveda, 2005;Sepú lveda et al, 2007). SPCAs also play a key task in Mn 2ϩ homeostasis, since they are the only known P-type ATPases that can transport Mn 2ϩ with high affinity (Van Baelen et al, 2001;Ton et al, 2002).…”

Alterations Induced by Ischemic Preconditioning on Secretory Pathways Ca2+-ATPase (SPCA) Gene Expression and Oxidative Damage After Global Cerebral Ischemia/Reperfusion in Rats

“…As shown by previous studies, the SPCA plays a pivotal role in normal neural development, neural migration, and morphogenesis (Sepúlveda et al 2007(Sepúlveda et al , 2008). In addition, as shown in SPCA1 knockout mice, SPCA1 deficiency caused alteration in neural tube development and Golgi stress.…”