Nerve Flashcards
Define retrograde movement
Movement of old components no endocytosis molecules from synapse to cell body for degradation/recycling
Anterograde Movement
Movement of molecules and protein in transport vesicles from cell body along axon
Features of Dyneins
Retrograde transport
>1,000,000kDa
Tail = cargo binding region
Motor unit consisting of:
Associated ATPase head
MTBD stalk
Globular heads bind dyne in to MT facilitated by MTBD
Requires association with dynactin acting as a co-factor to transport cargo
The dynactin complex consists of at least __ subnets.
8
List two important subunits of dynactin
- A short actin-related protein (Arq1) that binds dynamitin essential for cargo binding
- P150glued - a protein that binds MT
Kinesins can be…
…monomers, homodimers, heterodimers…
What are the two most important sites within a motor protein?
Motor and Tail
Kinesin motor protein features
Motor domain:
Beta sheet sandwiched between 2x alpha helices
Functions include microtubules binding, ATP binding, and ATP hydrolysis
Tail domain:
Binds cargo through transmembrane receptors
Motor protein walking
ATP head of MT binding domain binds Beta-tubulin
Release ATP
Trailing ADP end swings around in front of leading head
Binds new beta tubulin
ATP trailing head releases a phosphate to become ADP and unbinds the beta tubulin
Define proteostasis
Balancing of cellular pathways that are responsible for protein synthesis, folding, processing, assembly, trafficking, localisation and degradation.
What are the potential fates of newly synthesised proteins?
Chaperoned to either the ubiquities proteosome system or the autophagy lysosome pathway
What is ubiquitin?
A 76 amino acid protein that can be covalently linked to lysine residues of proteins targeted for Intracellular degradation by proteasomes.
What are proteasomes?
Multimeric proteases with a barrel shaped core and a cap that recognises polyubiquitinated proteins
Protein(s) associated with Parkinson’s disease
Alpha synuclein
Protein(s) associated with Alzheimer’s disease
Amyloid beta and Tau
Protein(s) associated with Multiple Taupathies
Tau (MT ass.)
Protein(s) associated with Huntington’s Disease
Huntingtin with tandem glutamine repeats
Features of Alzheimer’s disease
Degeneration of neurons, particularly in basal forebrain and hippocampus
Synaptic pathology and altered neuronal connections
Features of beta amyloid
Derived from proteolytic processing of amyloid precursor protein
Peptides come together to form amyloid fibrils with filamentous structure
2 kinds AB40 and AB42
Beta Amyloid Functions
Antimicrobial activity
Tumour suppression
Sealing leaks in blood brain barrier (BBB)
Promoting recovery from brain injury