Scientific Article
previous document  unige:11115  next document
add to browser collection

s-cyclophilin is retained intracellularly via a unique COOH-terminal sequence and colocalizes with the calcium storage protein calreticulin

Arber, S.
Caroni, P.
Published in The Journal of Cell Biology. 1992, vol. 116, no. 1, p. 113-125
Abstract Cyclophilins (cyclosporin A-binding proteins) are conserved, ubiquitous, and abundant proteins that accelerate the isomerization of XaaPro peptide bonds and the refolding of proteins in vitro. s-Cyclophilin is a member of the cyclophilin family with unique NH2- and COOH-terminal extensions, and with a signal sequence. We now report that s-cyclophilin is retained in the cell, and that the conserved s-cyclophilin-specific COOH-terminal extension VEKPFAIAKE is sufficient to direct a secretory protein to s-cyclophilin containing structures. Antibodies to s-cyclophilin-specific peptides were produced and the location of the protein was determined by an immunocytochemical study at the light microscopic level. s-Cyclophilin colocalized with the Ca(2+)-binding protein calreticulin and, to a lesser extent, with the microsomal Ca(2+)-ATPase in the myogenic cell line L6, and with the Ca(2+)-binding protein calsequestrin in skeletal muscle. In activated platelets, s-cyclophilin immunoreactivity was detected in a ring-like structure that might correspond to the Ca(2+)-storing and -releasing dense tubular network. In spreading cells, s-cyclophilin containing vesicular structures accumulated at actin-rich protrusion sites. While s-cyclophilin consistently codistributed with Ca2+ storage site markers, the distribution of s-cyclophilin immunoreactivity was not identical to that of ER markers. To determine whether the COOH-terminal extension of s-cyclophilin was involved in its intracellular transport we added this sequence to the COOH-terminus of the secretory protein glia-derived nexin. Appropriate constructs were expressed transiently in cultured cells and proteins were detected with specific antibodies. We found that glia-derived nexin with the COOH-terminal sequence VEKPFAIAKE (but not with the control sequence GLVVMNIT) colocalized with endogenous s-cyclophilin, indicating that the sequence contained retention information. These results indicate that s-cyclophilin is a retained component of an intracellular organelle and that it may accumulate in specialized portions of the ER, and possibly in calciosomes. Because of its conserved structure, widespread distribution, and abundance s-cyclophilin may be a useful marker to study the biogenesis and distribution of ER subcompartments.
Keywords Amino Acid Isomerases/analysis/genetics/ metabolismAmino Acid SequenceAnimalsAntibodiesCalcium-Binding Proteins/analysis/ metabolismCalcium-Transporting ATPases/analysisCalreticulinCarrier Proteins/analysis/genetics/ metabolismCell LineChickensCyclosporine/ metabolismEndocytosisEndoplasmic Reticulum/metabolism/ultrastructureHumansLiver/ metabolism/ultrastructureMolecular Sequence DataNocodazole/pharmacologyPeptides/chemical synthesis/immunologyPeptidylprolyl IsomeraseSequence Homology, Nucleic Acid
PMID: 1530944
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version:
(ISO format)
ARBER, S., KRAUSE, Karl-Heinz, CARONI, P. s-cyclophilin is retained intracellularly via a unique COOH-terminal sequence and colocalizes with the calcium storage protein calreticulin. In: The Journal of Cell Biology, 1992, vol. 116, n° 1, p. 113-125. doi: 10.1083/jcb.116.1.113

429 hits

0 download


Deposited on : 2010-08-27

Export document
Format :
Citation style :