Page 80 - Hematology_ Basic Principles and Practice ( PDFDrive )

52 Part I Molecular and Cellular Basis of Hematology

Plasma
Extracellular space membrane

Cytosol Regulated Constitutive
7 secretion 6 secretion 9 Endocytosis
Secretory Endocytic
vesicle vesicle
Sorting to
8
lysosomes

Trans-Golgi Late endosome
network Transport
vesicle

Lysosome
Trans-

Golgi stack Medial-
Retrograde transport from later
Cisternal progression 4 5 to earlier Golgi cisternae
Cis-

ERGIC
Retrograde Golgi-to-ER
3
Budding and fusion of transport
2 ER-to-Golgi vesicles
to form cis-Golgi

ER lumen
Rough ER

Protein synthesis on bound ribosomes:
1 cotranslational transport of proteins into
or across ER membrane
Fig. 5.4 PROTEIN TRAFFICKING THROUGH THE SECRETORY PATHWAY. The figure depicts the
secretory pathway starting from the endoplasmic reticulum (ER) (1) to the plasma membrane. Anterograde
ER-Golgi intermediate compartment (ERGIC) and retrograde ERGIC-ER transport are shown (2 and 3). The
transit through the Golgi apparatus is represented according to the cisternae progression and maturation model
described in the text (4 and 5). In the trans-Golgi the constitutive secretory pathway (6) and the regulated
secretory pathway (7) separate. In specialized secretory cells, selected proteins are sorted from the trans-Golgi
and diverted to secretory vesicles where proteins are stored until an extracellular signal triggers their fusion
with the plasma membrane and release of the content in the extracellular space (regulated exocytosis). In
addition, at the trans-Golgi proteins destined to the lysosome are sorted and delivered to the organelle through
vesicles (8). The endocytotic pathway (9) mediates the internalization of membrane or soluble extracellular
proteins and their targeting to the lysosome or the recycling of some proteins to the cell surface (not shown
in the figure).

PROCESSING OF PROTEINS IN THE ENDOPLASMIC start to fold cotranslationally by interaction with a host of chaperones,
among which is the Hsp70 family member BiP. In addition, there are
RETICULUM folding catalysts that increase the rate of protein folding. For example,
the proper pairing and formation of disulfide bonds is catalyzed by
Protein Folding in the Lumen of the ER oxidoreductases, such as protein disulfide isomerase (PDI), that also
shuffle nonnative disulfide bonds. In the current model, the oxidation
Protein chaperones facilitate protein folding in the ER, but amino of two thiols produces a disulfide bond (S–S) in the substrate protein
acid posttranslational modifications such as asparagine(N)-linked- and concomitantly reduces two thiols within PDI which return to
glycosylation and disulfide bond formation are also involved. Proteins the oxidized state by another thiol-disulfide exchange catalyzed by