This summary contains information about endosomes, endosome maturation, Rab5, Rab7, PI(3)P, sorting nexins, SNX-BAR domains, research/literature about the formation of tubules in the membrane, membrane curvature, liposome remodelling assay, retromers, and Alzheimer’s.
Experimental Cell Biology: Endosomal sorting
Learning objectives Inheriting the vacuolar domains of the EE
• You can describe the endosome system in network, which they combine during the journey
mammalian cells with newly synthesized lysosomal hydrolases and
• You can explain the different ways cells can membrane components from the secretory
bend lipid bilayers from a molecular perspective pathway. They need to deliver this mixture to
• You can explain how SNX-BAR proteins work lysosomes, but to do this they need to undergo a
in the cell maturation process that prepared them for the
• You can describe the link between retromer encounter. The endolysosome will be converted to
dysfunction and Alzheimer’s disease a dense lysosome which functions as a storage
organelle for lysosomal hydrolases and
Endosomes membrane components. Therefore pH in the
Endosomes are also called M lumen needs to go down from pH 7 to pH 5 and
multivesicular bodies there will also be a switch from Rab5 to Rab7a
(MVBs) and are the sorting which is needed for the maturation. What also
stations in the cell. The happens during endosome maturation is the
endosomal compartments phosphorylation of lipids (PI) in places 3,4 and 5.
sort membrane proteins by
incorporating them into Rab5 and Rab7a
vesicles. This process uses These are small GTPase proteins that play a
three multi-protein complexes. Endosomes are crucial role in endocytosis and membrane
pleomorphic organelles, which means that the transport.
cells (or nuclei) vary in size and shape.
Endosomes regulate the sorting of lipids and PI(3)P
membrane-bound proteins. Recycling of cargo Lipid phosphatidylinositol 3 -
(lipids and proteins) occurs in the tubular sub- phosphate are autophagic sensors,
domains of the maturing endosome. All content which are Conserved from yeast to
that is not sorted, is degraded in lysosomes. An humans.
endosome that fuses with a lysosome is called
an endolysosome. The endosome tubules thus Sorting nexins
function as different pathways. Sorting nexins are a large group of proteins that
are characterized by the presence of a phospho-
Endosome maturation lipid-binding domain. These proteins are involved
Late endosomes (LE) function as a system for in the process of protein sorting.
mediating the transport of lysosomal
components from the trans-Golgi network SNX-BAR domains
(TGN) to the lysosomes. The cargo that needs to The BAR domain is a protein dimerization motif
be sorted and recycled back to the plasma made up of three α-helixes that dimerize to form
membrane is transported via early endosomes a banana-shaped structure. This structure can
(EE). In most cells, around 50-180% of the modulate the phospholipid bilayer through
surface area of the plasma membrane is cycled electrostatic interactions. These interactions are
in and out of the cell every hour. The primary more associated with curved membranes rather
endocytic vesicles deliver their contents and than flat ones. In this way, BAR domains can
membrane to the EE in the peripheral sense membrane curvature. BAR domains are
cytoplasm. After some time during which the also able to drive membrane deformation by
EE’s accumulate cargo and forming helical arrays, thereby stabilizing the
Support recycling to the formation of high-curvature membrane tubules
Plasma membrane, and vesicles. Some BAR proteins contain
Conversion of the EE’s to additional membrane-binding modules to control
LE takes place. As the membrane association such as SNX.
Endosomes are moving
Towards the perinuclear
Space along microtubules,
The LEs are formed.
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