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* Department of Hematology, Lund University, Sweden;
Inflammation Program and Department of Medicine, Veterans Administration Medical Center and University of Iowa, Iowa City; and
The Netherlands Cancer Institute, Amsterdam
Correspondence: Elinor Bülow, M.D., Dept. of Hematology, C14, BMC, S-221 84 Lund, Sweden. E-mail: elinor.bulow{at}hematologi.lu.se
During formation of polymorphonuclear neutrophils, proteins are
synthesized for storage in granules. Whereas sorting of proteins into
distinct subtypes of cytoplasmic granules may reflect the coordinated
expression of the proteins contained in them, still the mechanism(s)
for the retrieval of proteins from the constitutive secretion is
unknown. To investigate the mechanisms of retrieval, nonmyeloid
secretory proteins were expressed in myeloid cell lines, and their
subcellular fate was assessed. The contribution of the propeptide
(MPOpro) of the myeloperoxidase (MPO) precursor was
investigated by determining the fate of chimeras containing MPOpro. The
nonmyeloid protein 
1-microglobulin (1-m)
was targeted to storage organelles in 32D cells and colocalized
with the lysosomal marker LAMP-1, whereas soluble TNF receptor 1
(sTNFR1) was secreted without granule targeting. Fusion of MPOpro to
1-m delayed exit from endoplasmic reticulum (ER), but
subsequent targeting to dense organelles was indistinguishable from
that of 1-m alone. Fusion proteins between MPOpro and
sTNFR1 or green fluorescent protein expressed in myeloid 32D, K562, or
PLB-985 cells did not associate stably with calreticulin or calnexin,
molecular chaperones that normally interact transiently with the MPO
precursor, but were still efficiently retained in the ER followed by
degradation. We conclude that normally secreted, nonmyeloid proteins
can be targeted efficiently to storage organelles in myeloid cells,
that myeloid cells selectively target some proteins for storage but not
others, and that MPOpro may contribute to the prolonged ER retention of
the MPO precursor independent of the ER-molecular chaperones
calreticulin and calnexin.
Key Words: neutrophil • granule • secretory pathway • 1-microglobulin • secretion
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