GTP-activated communication between distinct inositol 1,4,5-trisphosphate-sensitive and -insensitive calcium pools

Abstract

INOSITOL 1,4,5-trisphosphate (InsP₃) is an established mediator of intracellular Ca²⁺ signals¹ but little is known of the nature and organization of Ca²⁺ regulatory organelles responsive to InsP₃. Here we derive new information from the study of Ca²⁺ movements induced both by InsP₃ and a specific GTP-activated Ca²⁺ translocation process^2,3. The latter mechanism is clearly distinct from that activated by InsP₃ (ref. 4) and may involve the translocation of Ca²⁺ between compartments without its release into the cytosol^5-7. This idea is supported by the fact that GTP activates Ca²⁺ movement into the InsP₃-releasable pool^7,8. In the light of this evidence we postulated that there are two intracellular Ca²⁺ pools distinguishable by InsP₃-sensitivity and oxalate-permeability, and that movement between them is activated by GTP⁷. We report here direct evidence for the existence and separation of two distinct Ca²⁺-pumping compartments with properties coinciding with those predicted. Of these, the InsP₃-sensitive Ca²⁺ pool is identified within a purified rough endoplasmic reticulum fraction, an observation consistent with recent InsP₃ receptor-localization studies⁹. Ca²⁺ translocation between pools may reflect function of a class of small GTP-binding proteins known to mediate interorganelle transfer in eukaryotic cells¹⁰.