AD: Membraneless Organelles

P-bodies (processing bodies)

• consist of mRNA-decaying proteins and mRNA

Stress granules

• assemble under stress conditions

• function: redirect energy and resources for protection

Nucleolus

• redirection of energy and resources towards protection

• stabilization of mRNA secondary structures

• unwinding of double-stranded RNAs

• generally: nucleotide remodelling

• protein that aggregates accessively in amyotrophic lateral sclerosis (ALS)

• normally, FUS is transported into the nucleus via TPN1 (transportin)

• reasons:

  • mutation in the NLS of FUS

  • loss of Arg-methylation

  • mutation of specific arginine

lipid metabolism

PTS:

• PTS1: SKL at the C-terminus

  • recognized by PEX5

• PTS2: longer signal at N-terminus

  • recognized by PEX7

Import

• the target signal is recognized by PEX5/7

• complex binds to DTM (docking/translocation module)

• dissociation of PEX after import

• cleavage of PTS2 if present

Special in peroxisomes: Import and export have different canals.

Import: PEX13

• similar to NPC

• filled with YG phase

Export 1: PEX2-10-12

• ubiquitinylation of the protein as soon as it is exported to prevent re-import

Export 2: PEX1-6

• AAA+ ATPase