Calcium uptake via endocytosis with rapid release from acidifying endosomes

Abstract

A number of specific cellular Ca2+ uptake pathways have been described in many different cell types [1] [2] [3]. The possibility that substantial quantities of Ca2+ could be imported via endocytosis has essentially been ignored, although it has been recognized that endosomes can store Ca2+ [4] [5]. Exocrine cells can release significant amounts of Ca2+ via exocytosis [6], so we have investigated the fate of Ca2+ taken up via endocytosis into endosomes. Ca2+-sensitive and H+-sensitive fluorescent probes were placed in the extracellular solution and subsequently taken up into fibroblasts by endocytosis. Confocal microscopy was used to assess the distribution of fluorescence intensity. Ca2+ taken up by endocytosis was lost from the endosomes within a few minutes, over the same period as endosomal acidification took place. The acidification was inhibited by reducing the extracellular Ca2+ concentration, and Ca2+ loss from the endosomes was blocked by bafilomycin (100 nM), a specific inhibitor of the vacuolar proton ATPase. Quantitative evaluation indicated that endocytosis causes substantial import of Ca2+ because of rapid loss from early endosomes.

Infectious Bursal Disease Virus, a Non-enveloped Virus, Possesses a Capsid-associated Peptide That Deforms and Perforates Biological Membranes

“…Medium range NOE demonstrate that in DPC, pep46 is organized as four ␣-helices (amino acids 3 to 15 or (3-15)), (16 -22), (27)(28)(29)(30)(31)(32)(33), and (35-40) (Fig. 4, A and B 26 , His 30 confirms the cis/trans isomerization of several peptidyl-prolyl bonds.…”

Calmodulin protects against alcohol-induced pancreatic trypsinogen activation elicited via Ca 2+ release through IP 3 receptors

“…The principal compartment from which Ca 2+ can be liberated in pancreatic acinar cells is the ER (3). However, it has become clear in recent years that intracellular Ca 2+ pools in acid organelles also play important roles in intracellular Ca 2+ homeostasis (3,(23)(24)(25) and particularly do so in pancreatic acinar cells (12,18,19,26,27). Secretory (zymogen) granules (ZG) constitute a major part of the acid pool and contain large amounts of Ca 2+ (3).…”

Pancreatic protease activation by alcohol metabolite depends on Ca 2+ release via acid store IP 3 receptors

“…Important stores, from which Ca 2ϩ can be mobilized, have also been demonstrated in lysosomes and endosomes (17)(18)(19)(20)(21)(36)(37)(38)(39). Trypsin activation takes place in acid Baf-sensitive postexocytotic endocytic structures, which are, at least partially, co-localized with lysosomes (8).…”

“…Although the endoplasmic reticulum (ER) is the principal source of Ca 2ϩ released from internal stores in response to neurotransmitter or hormonal stimulation (3,15,16), Ca 2ϩ can also be liberated from acid stores (3,15,(17)(18)(19)(20)(21)(22). Several Ca 2ϩ -liberating agents release Ca 2ϩ from both thapsigargin (TG)-sensitive and bafilomycin (Baf)-sensitive acidic stores (21,22).…”