Neural Membranes Flashcards
What are two possible functions for hydrophobic domains of secretory pathway proteins?
1 . Signal sequence -> when protein is destined for secretion
2. Signal-anchor sequence -> when protein is meant to be transmembrane protein. Polytopic proteins will have multiple of these domains.
What are inclusion bodies?
Aggregates of misfolded proteins that are ubiquinated and awaiting degeneration via proteosomes, as well as some bystander proteins. They arise in the perinuclear region of cells.
How does the cell response to increased misfolded / unfolded protein levels?
It has a system to monitor these changes and independently signal.
Responses:
- General attenuation of translation
- Transcribe and translate molecular chaperones to refold.
- Degrade more unfolded proteins
If the above mechanisms do not work -> apoptosis, but maybe ischemia, oxidative stress, and inflammation
What do Schwann cells do which do not synthesize myelin sheaths?
They can surround a group of small axons to organize them in the periphery - called Remak bundles.
From where are Schwann cells and oligodendrocytes derived?
Schwann - Neural crest
Oligodendrocyte - ventral ventricular zone of neural tube, close to motor neuron progenitors
What are the major proteins in the CNS myelin?
- PLP - proteolipid protein, a transmembrane protein exclusive to CNS, similar to P0 in PNS
- MBP - Myelin Basic Protein - peripheral protein, very positively charged, holds adjacent negatively charged membranes together
What are the major proteins of the PNS myelin?
- P0 - Protein zero - transmembrane protein similar to PLP, a structural protein with positive charges to hold membranes together
- MBP - small amount, just like CNS
- PMP-22 - transmembrane protein with function unknown - defect cause of CMT type 1a
What do mutations in the PLP gene cause?
Leukodystrophy - destruction of white matter, as in Pelizaeus-Merzbacher disease, and spastic paraplegia
What do mutations in the PMP-22 gene cause?
Peripheral neuropathy, and Charcot-Marie-Tooth disease Type 1A
What do mutations in protein zero (P0) cause?
Charcot-Marie-Tooth disease Type 1B
What are the major dense line and IPL formed by?
These are the dark and light lines in CNS myelin.
Dark = major dense line = formed by inner membranes associating with no cytoplasm between them -> compact myeline
Light = IPL = intercellular line from fuses extracellular membranes but not as tightly opposed.
What is a lateral loop and what proteins hold it together structurally?
areas of cytoplasm outside compact myelin which contain cytoplasm, seen outside wrapping and at nodes of Ranvier.
Nodes are held together structurally by claudins which attach to adjacent myelin. Transmembrane proteins caspr and contactin hold myelin to axon. Band 4.1 holds the entire structure together within the axon.
How are myelin sheaths prevented from depolarizing at nodes of Ranvier? Why do we care?
There are K+ channels that hyperpolarize the membrane. You want to store as little charge as possible in myelin so that they are low capacitance, high resistance. Thus, the fields generated by Na+ channels on the axons can “jump” -> saltatory to affect a distant node of Ranvier.
What is the inheritance and effects of Pelizaeus-Merzebacher Disease (PMD)?
X-linked recessive -> boys get it more acutely. it’s a gain of function disease so carrier females will also be affected, but are usually subclinical, aside from mood disorders in later life due to unstable myelin breakdown later in life.
It is a leukodystrophy caused by mutation in PLP gene.
What is the range of clinical severity of PMD and what is the cause?
Mild: Paraparesis (mild paralysis of lower limbs), lower limb spasticity, normal life spine (similar to spastic paraplegia)
Severe: Quadriplegia, seizures, short life spine, widespread oligodendrocyte death
Mild: Deletions of PLP gene -> not critical for myelin
Severe: Duplication of normal PLP gene -> too much is really bad
Varied: Missense (wrong amino-acid) / nonsense (stop) mutations
