PMID- 7750518
OWN - NLM
STAT- MEDLINE
DCOM- 19950620
LR  - 20171116
IS  - 0171-9335 (Print)
IS  - 0171-9335 (Linking)
VI  - 66
IP  - 1
DP  - 1995 Jan
TI  - Regulated O-glycosylation of the Alzheimer beta-A4 amyloid precursor protein in 
      thyrocytes.
PG  - 39-46
AB  - In thyrocytes, the beta-amyloid precursor protein (beta-APP) is expressed, 
      proteolytically cleaved and released into the extracellular space in a 
      TSH-dependent fashion. Immunocytochemically, beta-APP was detectable mainly in 
      the stacked Golgi cisternae indicating the accumulation in this organelle. 
      Because this unusual immunoreactivity might be related to the Golgi-specific 
      posttranslational processing we studied the glycosylation of beta-APP and the 
      possible regulation of this process. For this purpose we used FRTL-5 cells which 
      showed that the degree of glycosylation was also TSH dependent. Glycosidase 
      digestion experiments revealed that only the O-glycans, not the N-glycans, of 
      beta-APP were regulated by TSH. Using enzyme digestion and lectin precipitation 
      analyses we showed that O-glycosylation involved mainly alpha 2,6-sialylated Gal 
      1-3 GalNAc-alpha-core glycans (approximately 85%) whereas the 2,3 linked sialic 
      acids amounted to only approximately 15% of total sialic acid residues. Upon 
      stimulation with TSH, O-glycosylation as measured by the degree of sialylation 
      increased by a factor of approximately 1.7 thereby raising the molecular mass of 
      mature beta-APP by 4 to 5 kDa above that from control cells. This process 
      coincided with the accumulation of a proteolytically derived 8.5 kDa C-terminal 
      beta-APP fragment indicating that the proteolytic processing of mature beta-APP 
      was not inhibited by its O-glycosylation. When cells were stimulated with TSH in 
      the presence of cycloheximide, the Golgi cisternae lost their predominant 
      immunoreactivity for beta-APP and were rapidly emptied (within 30 min). Hence, 
      under the conditions of normal protein synthesis, the Golgi cisternae may operate 
      as a storage compartment for beta-APP.
FAU - Graebert, K S
AU  - Graebert KS
AD  - Institut fur Zellbiologie, Rheinische Friedrich-Wilhelms-Universitat, 
      Bonn/Germany.
FAU - Popp, G M
AU  - Popp GM
FAU - Kehle, T
AU  - Kehle T
FAU - Herzog, V
AU  - Herzog V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Cell Biol
JT  - European journal of cell biology
JID - 7906240
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 9002-71-5 (Thyrotropin)
SB  - IM
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Cell Line
MH  - Cellular Senescence/drug effects
MH  - Glycosylation
MH  - Golgi Apparatus/chemistry
MH  - Stimulation, Chemical
MH  - Thyroid Gland/cytology/*drug effects/metabolism
MH  - Thyrotropin/*pharmacology
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
PST - ppublish
SO  - Eur J Cell Biol. 1995 Jan;66(1):39-46.