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NoMembraneOrganelles

Membraneless Organelles

QuestionAnswer
What are membraneless organelles? Liquid droplets
Functions of membraneless organelles? (3) 1. Store molecules 2. Form reaction crucibles 3. Organise cellular functions
What mediates droplet formation? A scaffold of protein & RNA
Proteome of membraneless organelles? Dominated by proteins with intrinsically disordered regions
What does the scaffold do? Recruits client proteins to the droplets
Liquid-to-solid phase transitions cells? Associated with disease
Give some examples of membraneless organelles please (9 max) 1. Nucleolus 2. Paraspeckle 3. Nuclear speckle 4. Cajal bodies 5. PML bodies 6. P bodies 7. Stress granules 8. Germ granules 9. Balbiana body
What do P granules do in germ line cells? 'Drip' around nucleus
What do P bodies to in germ line cell division? All go to one daughter cell - this is the progenitor germ cell
Define FRAP Fluorescence Recovery after Photobleaching
Things that droplets do? (3) 1. Reaction crucible 2. Sequestration 3. Organisational hub
How are droplet molecules formed? Liquid-Liquid Phase Separation
Dispersed vs concentrated state dispersed - proteins interact w/ water concentrated - protein-protein interactions (in droplets)
When is low entropy favoured? When protein-protein interaction of favoured over protein-water interaction
What is high entropy? High disorder - molecules arranged randomly
When does demixing occur? When homotypic interactions energies are more favourable than heterotypic interaction energies
What type of proteins drive LLPS? Multivalent proteins with IDRs (Intrinsically Disordered Regions)
What is a protein with an Intrinsically Disordered Region (IDR)? Functional protein without unique structure
What is C-critical? The concentration at which a protein will form droplets
What can the C-critical be modified by? (3) 1. PTMs 2. Temperature 3. Ionic strength
What are scaffolds & clients? Key set of proteins & RNA that drive membraneless organelle formation
What do stress granules contain? (3) 1. PICs (mRNA stalled in translation initiation) 2. Translation Initiation Factors 3. RNA-binding proteins, non-RNA-binding proteins
Stress granule functions? (2) 1. Control utilisation of mRNA during stress 2. Implicated in diseases
Stress granule assembly? (3) 1. PIC formed (mRNA + 40S ribosome complex) 2. Accumulation of complex 3. 40S-mRNA complexes associate w/ RBPs that nucleate SG formation
What does inhibiting translation initiation do? Promotes formation of stress granules
Cycle of Stress Granule formation? (4) 1. Nuclear RBPs (RNA-bind.prot.) translocated to cytoplasm 2. SG nucleation 3. SGs mature - recruit other RBPs 4. SGs disperse, soluble RBPs to nucleus, not solid RBPs disposed by autophagosomes
Liquid-solid transition of SG proteins under ACUTE stress RBPs assemble into SGs - aggregates associated w/ disease seed formation of these
Liquid-solid transition of SG proteins under CHRONIC stress liquid assemblies become gel-like aggregates - TDP-43 becomes phosphorylated
Liquid-solid transition of SG proteins when stress resolved things happen but pathological aggregates remain
What is TDP-43? binding protein - phosphorylation associated w/ disease
What does TDP-43 form? Amyloid fibrils
Phase separation in neurodegeneration please (4) 1. Trapping of cellular factors 2. Mutations/repeat expansions 3. Abnormal PTMs 4. Aberrant condensates & liquid-solid transitions
Phase separation in cancer please Mutations in signalling receptors alter signalling clusters at sites of transcription/DNA damage repair
Phase separation in infectious disease Viral factories - liquid-like condensates early infection - dissolved by 1-6-hexanediol late infection - SOLID - cannot be dissolved
Created by: rubyroo
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