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Eukaryotic Cell, February 2004, p. 52-60, Vol. 3, No. 1
1535-9778/04/$08.00+0 DOI: 10.1128/EC.3.1.52-60.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
-COP Affects Functioning of Secretory Organelles and Calcium Homeostasis in Hansenula polymorpha
Institute of Experimental Cardiology, Cardiology Research Center, 121552 Moscow, Russia
Received 19 July 2003/ Accepted 27 October 2003
In eukaryotic cells, COPI vesicles retrieve resident proteins to the endoplasmic reticulum and mediate intra-Golgi transport. Here, we studied the Hansenula polymorpha homologue of the Saccharomyces cerevisiae RET1 gene, encoding
-COP, a subunit of the COPI protein complex. H. polymorpha ret1 mutants, which expressed truncated
-COP lacking more than 300 C-terminal amino acids, manifested an enhanced ability to secrete human urokinase-type plasminogen activator (uPA) and an inability to grow with a shortage of Ca2+ ions, whereas a lack of
-COP expression was lethal. The
-COP defect also caused alteration of intracellular transport of the glycosylphosphatidylinositol-anchored protein Gas1p, secretion of abnormal uPA forms, and reductions in the levels of Pmr1p, a Golgi Ca2+-ATPase. Overexpression of Pmr1p suppressed some ret1 mutant phenotypes, namely, Ca2+ dependence and enhanced uPA secretion. The role of COPI-dependent vesicular transport in cellular Ca2+ homeostasis is discussed.
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