The organisation of intracellular traffic - endocytic pathway
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What is the main function of the endosomal system?
To sort internalised material and membrane proteins for recycling, degradation, or retrograde transport to other organelles.
Which major pathways feed into the endosomal system?
Endocytosis from the plasma membrane, biosynthetic input from the Golgi, and autophagy-derived vesicles.
What determines the fate of internalised cargo?
Sequential sorting steps governed by compartment identity markers such as Rab GTPases, phosphoinositides, and pH.
What are the three main fates of endocytosed cargo?
(1) Recycling to plasma membrane, (2) Degradation in lysosomes, (3) Retrograde trafficking to the Golgi/TGN.
What is the endosomal maturation process?
Progressive conversion of early to late endosomes involving Rab and phosphoinositide changes, lumen acidification, and cargo sorting.
Which organelle do endosomes fuse with for degradation?
Lysosomes.
What is the defining biochemical difference between early and late endosomes?
Early endosomes are Rab5 and PI(3)P positive; late endosomes are Rab7 and PI(3,5)P₂ positive.
Why is acidification important in endosomal maturation?
It facilitates cargo dissociation, receptor recycling, and activation of degradative enzymes.
What pump drives endosomal acidification?
The vacuolar-type ATPase (V-ATPase).
What are endosomal carrier vesicles (ECVs)?
Tubular or vesicular intermediates that form during maturation, mediating transfer between endosomal stages.
What Rab defines early endosomes?
Rab5.
How is Rab5 activated?
By its GEF Rabex-5.
What happens when Rab5 is activated?
It recruits effectors promoting membrane tethering, fusion, and endosomal identity.
Name Rab5 effectors.
EEA1, Rabaptin-5, and PI3-kinase VPS34 complex.
What does EEA1 do?
Tethers Rab5-positive membranes for early endosome fusion.
Which phosphoinositide defines early endosomes?
PI(3)P.
How is PI(3)P generated?
By class III PI3-kinase VPS34.
What is the function of PI(3)P?
Recruits FYVE- or PX-domain proteins such as EEA1, Hrs, and SNX family proteins.
What initiates Rab5 to Rab7 conversion?
Activation of the Mon1–Ccz1 complex, which displaces Rabex-5 and activates Rab7.
What is Rab conversion?
Sequential replacement of Rab5 by Rab7, switching endosomal identity and function.
What Rab defines late endosomes?
Rab7.
How is Rab7 recruited?
By the Mon1–Ccz1 complex.
What is Rab7’s role?
Regulates late endosome transport and fusion with lysosomes.
Which motor proteins interact with Rab7?
Dynein (minus-end) and kinesins (plus-end).