#secretory pathway

Cell Organelles

The Golgi apparatus is responsible for:

Golgi apparatus comprises four to eight flattened cisternae forming cis entry, medial processing and trans exit network with distinct enzyme gradients maintaining glycosylation sequence. Cargo arriving via COPII vesicles from ER undergoes mannose trimming by mannosidase I in cis, addition of N-acetylglucosamine by GlcNAc transferase I and II in medial, galactose and sialic acid in trans, creating complex glycans affecting half-life and receptor binding. Phosphorylation of mannose residues marks lysosomal enzymes, sulfation of proteoglycans occurs. Trans-Golgi network functions as major sorting

Ref: Rothman Cell 1994; Golgi cisternae glycosylation phosphorylation sorting TGN clathrin AP1 GGA.

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Protein Sorting and Trafficking

Which of the following best describes the pathway of secretory proteins?

Classical secretory pathway described by George Palade using pulse-chase autoradiography follows polarized itinerary from synthesis to release. Proteins destined for secretion start on rough ER where N-terminal signal peptide directs co-translational insertion via Sec61 channel and cleavage by signal peptidase. Core N-glycosylation, chaperone assisted folding and disulfide formation occur there before concentration at ER exit sites organized by Sec16 and COPII coat assembly controlled by Sar1 GTPase. Vesicles form ER-Golgi intermediate compartment and fuse into cis-Golgi cisterna. Cargo then t

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 14: Secretory Pathway ER to Golgi to PM.

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Protein Sorting and Trafficking

Which transport mechanism involves translocons?

Translocons are aqueous protein-conducting channels allowing hydrophilic polypeptide chains to cross hydrophobic lipid bilayers. Classic examples include Sec61 complex in mammalian ER and SecYEG in bacteria, hourglass pores with plug helix and lateral gate opening to membrane for integration of stop-transfer sequences. Mitochondria possess distinct but conceptually analogous translocons: TOM complex in outer membrane with Tom40 beta-barrel channel, receptors Tom20 recognizing amphipathic presequences and Tom70 for hydrophobic carriers, and small Toms regulating assembly; TIM23 complex in inner

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 12: TOM-TIM and Sec61 Translocons.

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Protein Sorting and Trafficking

Which experiment first demonstrated the secretory pathway of protein trafficking?

Historical demonstration of secretory pathway utilized pulse-chase labeling paradigm coupled to electron microscopic autoradiography introduced by Nobel laureate George Palade. Model tissue pancreatic acinar cells specialized for massive secretion of digestive enzymes such as amylase, trypsinogen, chymotrypsinogen provided high signal. Tissue slices pulsed briefly for few minutes with tritiated leucine 3H-leucine incorporated into nascent polypeptides in rough endoplasmic reticulum, then chased with large excess non-radioactive leucine preventing further labeling enabling tracking of labeled c

Ref: Palade, Science 1975, Intracellular Transport. Alberts 7th ed., Chapter 12, Secretory Pathway History.

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