Curriculum
Module 04 · 70 min
Organelles & the Secretory Pathway
ER, Golgi, lysosomes, and the COP/clathrin logistics network that keeps a cell alive.
CoreClinicalResearch
Topics
What this module covers
- 01Co-translational ER targeting: SRP, Sec61, signal peptides
- 02N-glycosylation, calnexin/calreticulin cycle
- 03COPII (ER → Golgi), COPI (retrograde), clathrin (post-Golgi/endocytosis)
- 04Rab GTPases as identity tags; SNAREs for fusion
- 05Lysosomes: hydrolases, mTORC1 platform, lysosomal storage diseases
- 06Mitochondrial protein import (TOM/TIM); peroxisome biogenesis
Deep dives
Lesson sub-pages
Learning objectives
By the end of this module you will be able to
- L01Trace a secreted protein from ribosome to extracellular space, naming the machinery at each step.
- L02Explain why a single missing lysosomal hydrolase produces a pleiotropic, often neurological, disease.
- L03Distinguish COPI, COPII, and clathrin coats by location, cargo, and triggering GTPase.
Expected takeaways
What you should walk away believing
- →Vesicle traffic is GTPase-regulated identity logistics; misrouting causes disease.
- →Lysosomal storage diseases are model 'one missing enzyme, system-wide failure' diseases.
- →Mitochondrial import is post-translational and energy-dependent — a vulnerability in many myopathies.
Core summary
At the Core level
About a third of all human proteins enter the secretory pathway. They are made on ER-bound ribosomes, glycosylated and quality-checked in the ER, sorted in the Golgi, and dispatched in vesicles bearing identity tags (Rabs) that dock and fuse via SNAREs. Lysosomes terminate this stream and feed nutrients back to mTORC1.
Myth vs reality
Common misconception
Claim
All proteins are translated on free cytosolic ribosomes.
Reality
About one third of human proteins are co-translationally targeted to the ER; mistargeting is a recognised disease mechanism.
Evidence-graded claims
Claims, scored A–F
A
Mannose-6-phosphate is the canonical lysosomal targeting tag for soluble hydrolases
Established cell biology.
A
Rab GTPases mark organelle identity
>60 Rabs each defining specific compartments.
F
Eliglustat cures Gaucher disease
It reduces substrate accumulation; not curative.
Quiz
Check your understanding
Q1. Which coat protein mediates ER → Golgi transport?
Q2. I-cell disease results from defective:
Flashcards
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Front
SRP function?
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Suggested reading
Primary literature
- The cell biology of secretion — Lippincott-Schwartz & Phair, Annu Rev Biophys 2010 ↗
- Lysosomal storage diseases — Platt et al., Nat Rev Dis Primers 2018 ↗