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Publikationen
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GLYOKOPROTEINMUSTER
IN OVARIALEN ZYSTENINHALTEN; K.Czerwenka, K.Kremser & H.Retzek;
Gyn.Rundschau 26, 293-294 (1986)
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CHARACTERIZATION OF CHYLOMICRON
REMNANT UPTAKE IN RAT LIVER; M.Hüttinger,
H.Retzek, M.Eder
& H.Goldenberg; Clin. Biochem., Vol 21, pp. 87-92, 1988
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UPTAKE AND SUBCELLULAR DISTRIBUTION
OF INJECTED TRANSFERRIN IN RAT LIVER; H.Goldenberg, M.Eder, R.Pumm, E.Wallner,
H.Retzek
&
M.Hüttinger; Biochim.Biophys.Acta 968, 331-339 (1988)
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LACTOFERRIN SPECIFICALLY INHIBITS
ENDOCYTOSIS OF CHYLOMICRON REMNANTS BUT NOT -MACROGLOBULIN; M. Huettinger,
Helmut
Retzek, M. Hermann & H. Goldenberg; J. Biol. Chem. Vol. 267, pp.18551-18557
(1992)
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MOLECULAR CLONING AND FUNCTIONAL
CHARACTERIZATION OF CHICKEN CATHEPSIN D, A KEY ENZYME FOR YOLK FORMATION;
H.Retzek, E. Steyrer, E.J.Sanders, J. Nimpf & W.J.Schneider, DNA
and cell biology 11(9) (1992 Nov) :661-72
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CHICKEN OOCYTE GROWTH: RECEPTOR-MEDIATED
YOLK DEPOSITION; X. Shen, E. Steyrer, H. Retzek, E.J. Sanders &
W.J. Schneider; (1993) Cell Tissue Res 272:459-471
Abstrakts
& Konferenz-Beiträge
-
GLYOKOPROTEINMUSTER
VON OVARIALEN (NEOPLASTISCHEN) ZYSTENINHALTEN MITTELS DER "LEKTINBLOTTING"
- METHODE; K.Czerwenka, K.Kremser & H.Retzek; Jahrestagung der
Österreichischen Gesellschaft f. Gynäkologie und Geburtshilfe,
Eisenstadt, 29.-31. Mai 1986; Abstracts 103
-
HEPATISCHE AUFNAHME VON CHYLOMICRON
REMNANTS: EINFLUß DES GLYCOPROTEIN LAKTOFERRIN; M.Huettinger, H.Retzek,
H.Goldenberg, Vortragsreihe der Gesellschaft der Ärzte, Wien, März
1988
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LACTOFERRIN BLOCKS ENDOCYTOSIS
OF CMR (CHYLOMICRON REMNANTS) BUT NOT LDL (LOW DENSITY LIPOPROTEIN); M.Huettinger,
H.Retzek,
H.Auer & M.Valyon; 4th International Congess of Cell Biology, 14-19
August, 1988 Montreal, Abstracts P6.2.26, p 188
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SPECIFIC INHIBITORY ACTION OF
LACTOFERRIN ON HEPATIC CHYLOMICRON REMNANT UPTAKE; M.Huettinger, H.Retzek;
11th European Lipoprotein Conference, 11.-14. September, 1988;
Tutzing, BRG, Abstracts
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INHIBITION OF ENDOCYTOSIS OF
CHYLOMICRON REMNANTS BY LACTOFERRIN; M.Huettinger,
H.Retzek
&
H.Goldenberg; International Atherosclerosis Congress 20.-22. April, 1989
Vienna, Abstracts (128) p 24
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INHIBITION OF ENDOCYTOSIS
OF CHYLOMICRON REMNANTS BY LACTO-FERRIN; H.Retzek & M.Hüttinger;
Hepatic Cholesterol & Lipoprotein Conference, 19.-22. August, 1989
Aspen/Colorado
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Uptake and subcellular distribution of
injected transferrin in rat liver.
Goldenberg H, Eder M, Pumm R, Wallner E, Retzek H, Huttinger M
Department of Medical Chemistry, University of Vienna, Austria.
Radioactively labelled transferrin was injected into rats intravenously and
its uptake and subcellular distribution in the liver was investigated. The
amount of radioactivity in the liver remained constant from 10 min after
injection. It was not influenced by asialoglycoproteins. The radioactive
label was identified as asialotransferrin. After subcellular fractionation
by differential and zonal sucrose density-gradient centrifugation the label
was enriched in a low-density endocytic compartment showing fluorescence
quenching of acridine orange and N-ethylmaleimide-sensitive ATPase activity.
The data fit into a model of continuous transferrin-receptor-mediated
recycling through the hepatocyte's endocytic compartment.
PMID: 2449912
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Molecular cloning and functional
characterization of chicken cathepsin D, a key enzyme for yolk formation.
Retzek H, Steyrer E, Sanders EJ, Nimpf J, Schneider WJ
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Upon receptor-mediated endocytosis of very-low-density lipoprotein (VLDL)
and vitellogenin into growing chicken oocytes, the protein moieties of these
lipoproteins are proteolytically cleaved. Unlike the complete lysosomal
degradation in somatic cells, enzymatic ligand breakdown in oocytes
generates a characteristic set of polypeptides, which enter yolk storage
compartments for subsequent utilization by the embryo. Here, we demonstrate
directly that the catalyst for the intraoocytic processing of both
apolipoprotein B and vitellogenin is cathepsin D. The enzyme was purified
from oocytic yolk, preovulatory follicle homogenates, and liver by affinity
chromatography. When plasma VLDL and vitellogenin were incubated with the
purified enzyme, fragments indistinguishable from those found in yolk were
generated from both precursors under identical, mildly acidic conditions.
Amino-terminal sequencing of the pure enzyme demonstrated 88% identity with
mammalian cathepsin Ds over 34 residues. On the basis of this information, a
full-length clone specifying chicken preprocathepsin D was isolated from a
chicken follicle cDNA library by screening with a human cathepsin D probe.
Whereas previous studies have demonstrated that the receptors for
lipoproteins in somatic cells and oocytes, respectively, of the chicken are
the products of different genes, Southern and Northern blot hybridization
experiments showed that the enzymes expressed in oocytes and liver are the
product of a single gene, giving rise to a 3.3-kb transcript. The primary
structure of the 335-residue mature protein suggests a high degree of
conservation of known crucial features of aspartyl proteases; however, the
absence of the so-called processing region and of an aromatic residue in a
region thought to partake in catalysis raise questions with possible
evolutionary implications.
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Characteristics of chylomicron
remnant uptake into rat liver.
Huettinger M, Retzek H, Eder M, Goldenberg H
University of Vienna, Department of Medical Chemistry, Austria.
We have investigated uptake of 125I-labeled chylomicron remnants into livers
of rats in the presence of lactoferrin. This glycoprotein possesses a
cluster of four arginines at the N-terminus similar to the arginine rich
binding sequence of apoprotein E (apoE) to the LDL-receptor. We found that
this protein inhibits uptake of 125I-chylomicron remnant radioactivity by
50% when measured as accumulation of radioactivity into the intact organ,
and even more pronounced, over 75%, when measured as uptake into an
endosomal fraction prepared therefrom. Provided that the arginine rich
sequence is responsible for the inhibition, a similarity in the
characteristics of binding of apoE to the LDL (low density lipoprotein)- and
chylomicron remnant-receptor is likely. Second, transferrin having sequence
homologies with lactoferrin, but lacking the arginine cluster does not
interfere with chylomicron remnant uptake. Third, lactoferrin does not
inhibit the uptake of chylomicron remnants by the spleen, which is most
likely mediated through scavenger cells by a mechanism different from the
chylomicron remnant uptake system of the liver. We hypothesize from this
that lactoferrin specifically interferes with the physiologically relevant
chylomicron remnant uptake system of the liver. Investigation of the
mechanism of this inhibition will provide information about the physical
characteristics of the remnant receptor system.
PMID: 3390901
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Chicken oocyte growth:
receptor-mediated yolk deposition.
Shen X, Steyrer E, Retzek H, Sanders EJ, Schneider WJ
Department of Medicine, University of Manitoba, Winnipeg, Canada.
During the rapid final stage of growth, chicken oocytes take up massive
amounts of plasma components and convert them to yolk. The oocyte expresses
a receptor that binds both major yolk lipoprotein precursors, vitellogenin (VTG)
and very low density lipoprotein (VLDL). In the present study, in vivo
transport tracing methodology, isolation of coated vesicles, ligand- and
immuno-blotting, and ultrastructural immunocytochemistry were used for the
analysis of receptor-mediated yolk formation. The VTG/VLDL receptor was
identified in coated profiles in the oocyte periphery, in isolated coated
vesicles, and within vesicular compartments both outside and inside
membrane-bounded yolk storage organelles (yolk spheres). VLDL particles
colocalized with the receptor, as demonstrated by ultrastructural
visualization of VLDL-gold following intravenous administration, as well as
by immunocytochemical analysis with antibodies to VLDL. Lipoprotein
particles were shown to reach the oocyte surface by passage across the
basement membrane, which possibly plays an active and selective role in yolk
precursor accessibility to the oocyte surface, and through gaps between the
follicular granulosa cells. Following delivery of ligands from the plasma
membrane into yolk spheres, proteolytic processing of VTG and VLDL by
cathepsin D appears to correlate with segregation of receptors and ligands
which enter disparate sub-compartments within the yolk spheres. In small,
quiescent oocytes, the VTG/VLDL receptor was localized to the central
portion of the cell. At onset of the rapid growth phase, it appears that
this pre-existing pool of receptors redistributes to the peripheral region,
thereby initiating yolk formation. Such a redistribution mechanism would
obliterate the need for de novo synthesis of receptors when the oocyte's
energy expenditure is to be utilized for plasma membrane synthesis,
establishment and maintenance of intracellular topography and yolk formation,
and preparation for ovulation.
PMID: 8393385
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Lactoferrin specifically inhibits
endocytosis of chylomicron remnants but not alpha-macroglobulin.
Huettinger M, Retzek H, Hermann M, Goldenberg H
Department of Medical Chemistry, University of Vienna, Austria.
Our recently found nonlipoprotein inhibitor of chylomicron remnant uptake,
lactoferrin, has been investigated in vivo and in vitro. Lipoprotein lipase
extracted triglycerides from chylomicrons, doubly labeled with
[3H]retinol/[14C]oleate, in the presence of lactoferrin normally. The
subsequent uptake of remnants into liver was retarded considerably. In the
intact rat, chylomicron remnants (CRs), predominantly labeled in the apoB48
moiety by 125I, were excluded from the hepatic endosomal compartment in the
presence of lactoferrin as shown in subcellular fractionation studies of rat
livers. In tissue culture, internalization of [125I]chylomicron remnants was
inhibited in the presence of 14 pM lactoferrin by 70%. Upon removal of
lactoferrin, internalization was rapidly restored. Protease digestion
eliminated the inhibitory effect completely. Modification of arginine
residues with cyclohexanedione reversibly removed the inhibitory potency of
lactoferrin. We located by molecular modeling an alpha-helical segment in
lactoferrin on the exposed surface of the molecule containing the sequence
Arg-X-X-Arg-Lys-X-Arg, which resembles the receptor recognition structure in
apolipoprotein E (apoE). This firmly established ligand correspondence with
apoE, the candidate ligand for CR recognition by the receptor. Finally, the
postulated second function of low density lipoprotein receptor-related
protein, uptake of alpha-2-macroglobulin (alpha 2M) was found to be distinct
from lipoprotein binding, since lactoferrin inhibited CR but not alpha 2M
internalization. In addition, CR uptake was not affected by alpha 2M. We
conclude that if a bifunctional receptor were to operate, its diverse
functions were exerted by independently operating substructures. The results
of our in vivo and cell culture experiments are, however, entirely
compatible with the existence of two receptors as well.
PMID: 1382056
Cloning
Result of Chicken Cathepsin D
SWISS-PROT:
Q05744
NiceProt - a user-friendly view
of this SWISS-PROT entry
ID CATD_CHICK
STANDARD; PRT; 398 AA.
AC Q05744;
DT 01-FEB-1994 (REL.
28, CREATED)
DT 01-FEB-1994 (REL.
28, LAST SEQUENCE UPDATE)
DT 01-NOV-1995 (REL.
32, LAST ANNOTATION UPDATE)
DE CATHEPSIN D PRECURSOR
(EC 3.4.23.5).
OS GALLUS GALLUS (CHICKEN).
OC EUKARYOTA; METAZOA;
CHORDATA; VERTEBRATA; ARCHOSAURIA; AVES;
OC NEOGNATHAE; GALLIFORMES;
PHASIANIDAE; PHASIANINAE; GALLUS.
RN [1]
RP SEQUENCE FROM N.A.,
AND SEQUENCE OF 64-97.
RC TISSUE=FOLLICLE;
RX MEDLINE; 93039672.
[NCBI, ExPASy, Israel, Japan]
RA RETZEK
H., STEYRER E., SANDERS E.J., NIMPF
J., SCHNEIDER W.J.;
RT "Molecular cloning
and functional characterization of chicken
RT cathepsin D, a key
enzyme for yolk formation.";
RL DNA CELL BIOL. 11:661-672(1992).
CC -!- FUNCTION: CATHEPSIN
D IS AN ACID PROTEASE ACTIVE IN INTRACELLULAR
CC
PROTEIN BREAKDOWN. IN CHICKEN IT IS A KEY ENZYME FOR YOLK
CC
FORMATION AS IT IS CAPABLE OF CATALYZING INTRA OOCYTIC BREAK DOWN
CC
OF PROTEIN COMPONENTS OF BOTH VITELLOGENIN AND VLDL.
CC -!- SUBUNIT: CONSISTS
OF A LIGHT CHAIN AND A HEAVY CHAIN.
CC -!- SUBCELLULAR
LOCATION: LYSOSOMAL.
CC -!- TISSUE SPECIFICITY:
OOCYTIC YOLK, PREOVULATORY FOLLICLES, LIVER.
CC -!- SIMILARITY:
BELONGS TO PEPTIDASE FAMILY A1; ALSO KNOWN AS THE
CC
EUKARYOTIC ASPARTYL PROTEASES FAMILY.
CC --------------------------------------------------------------------------
CC This SWISS-PROT
entry is copyright. It is produced through a collaboration
CC between the
Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics
Institute. There are no restrictions on its
CC use by
non-profit institutions as long as its content is
in no way
CC modified and this
statement is not removed. Usage by and for commercial
CC entities requires
a license agreement (See http://www.isb-sib.ch/announce/
CC or send an email
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DR EMBL; S49650; AAB24157.1;
-. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR PROSITE; PS00141;
ASP_PROTEASE; 2.
DR PFAM; PF00026; asp;
1.
DR HSSP; P07339; 1LYA.
[HSSP ENTRY / SWISS-3DIMAGE /
DR
PDB-ENTRY / PDB-RASMOL / PDB-3DIMAGE]
DR DOMO; Q05744.
DR PRODOM [Domain structure
/ List of seq. sharing at least 1 domain]
DR PROTOMAP; Q05744.
DR PRESAGE; Q05744.
DR SWISS-2DPAGE; GET
REGION ON 2D PAGE.
KW HYDROLASE; ASPARTYL
PROTEASE; GLYCOPROTEIN; LYSOSOME; SIGNAL; ZYMOGEN.
FT SIGNAL
1 20 POTENTIAL.
FT PROPEP
21 63 ACTIVATION
PEPTIDE (POTENTIAL).
FT CHAIN
64 398 CATHEPSIN
D.
FT CHAIN
64 157 LIGHT CHAIN
(PROBABLE).
FT CHAIN
158 398 HEAVY CHAIN
(PROBABLE).
FT ACT_SITE
96 96 BY SIMILARITY.
FT ACT_SITE
283 283 BY SIMILARITY.
FT DISULFID
109 116 BY SIMILARITY.
FT DISULFID
274 278 BY SIMILARITY.
FT DISULFID
317 354 BY SIMILARITY.
FT CARBOHYD
133 133 POTENTIAL.
FT CARBOHYD
251 251 POTENTIAL.
SQ SEQUENCE
398 AA; 43298 MW; A45111DE CRC32;
MAPRGLLVLL
LLALVGPCAA LIRIPLTKFT STRRMLTEVG SEIPDMNAIT QFLKFKLGFA
DLAEPTPEIL
KNYMDAQYYG EIGIGTPPQK FTVVFDTGSS NLWVPSVHCH LLDIACLLHH
KYDASKSSTY
VENGTEFAIH YGTGSLSGFL SQDTVTLGNL KIKNQIFGEA VKQPGITFIA
AKFDGILGMA
FPRISVDKVT PFFDNVMQQK LIEKNIFSFY LNRDPTAQPG GELLLGGTDP
KYYSGDFSWV
NVTRKAYWQV HMDSVDVANG LTLCKGGCEA IVDTGTSLIT GPTKEVKELQ
TAIGAKPLIK
GQYVISCDKI SSLPVVTLML GGKPYQLTGE QYVFKVSAQG ETICLSGFSG
LDVPPPGGPL
WILGDVFIGP YYTVFDRDND SVGFAKCV
//
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Heli Retzek <heli.retzek@aon.at>
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