ER and Golgi Stress (Lecture 5)

What are prolonged ER and Golgi stress linked to?

• Neurodegeneration

• Diabetes

• Cancer

Primary Gigi processing disorder

Defect in the golgi is the root cause of the illness

• ex: mutations in Golgi proteins

Secondary Golgi processing disorder

The disease causes stress/dysfunction in the Golgi apparatus

• misfolded protein trying to get through Golgi and clogging it up

What is Complex Vertebral Malformation?

A primary Golgi processing disorder that affects Holstein and Montbeliarde cattle that causes defective transport of sugar-nucleotides into the Golgi lumen leading to impaired glycosylation of proteins and results in skeletal malformations (rib and vertebrae), abortions, death.

What is Alpha-mannosidosis?

A secondary Golgi-processing disorder that causes death within the first year of life; symptoms include neurological deficits, growth & skeletal abnormalities, sensory impairment, immune system weakened that affects Cats (DLH, DSH, Persian), Dogs (Doberman), Cattle (Angus, Galloway, Murray Grey), and Guinea Pigs

What gene is mutated in alpha-mannosidoisis?

MAN2B1

What happens in alpha-mannosidosis biologically?

Misfolded MAN2B1 cannot undergo correct Golgi processing or retained in ER meaning it fails to acquire proper trimming or M6P modification

Misfolding of SLC3A1 or SLC7A9 causes what?

ER retention classifying cystinuria as a secondary ER-processing disorder

What is a lysosome?

The cell’s recycling center that contains nucleuses, proteases, phosphatases, known as acid hydrolases that carries out degradation of mutated/misfolded proteins from the Golgi and damaged organelles through autophagy

Endocytosis

Process of moving proteins, viruses, and other macromolecules from intracellular spaces and form endosomes

Phagocytosis

Large insoluble particles (bacteria) are internalized by plasma membrane; form phagosome

What is Lysosomal Storage Disease?

Alpha-mannosidoisis - single gene disorder that is fatal (no treatments)

What is a peroxisome?

Organelles that are vital for cellular metabolism that do fatty acid oxidation, lipid biosynthesis, and detoxification

Fatty Acid Oxidation

peroxisomes breakdown various fatty acids for energy production and cell function

Lipid Biosynthesis

Involved in synthesizing specialized lipids (bile acids)

Detoxification

Enzyme catalase that breaks down hydrogen peroxide into harmless oxygen and water

What is Rhizomelic Chondrodysplasia Punctata?

A peroxisome disorder that affects Aubrey cattle from a mutation in GNPAT and causes slowed growth, death, spontaneous abortion, epiphyseal stippling, dysmorphic craniofacial features and limb shortening

What is special about the mitochondria?

• Contains its own genome

• Double membrane

• Powerhouse of the cell

• Quantity can vary depending on cell types

What are the functions of the nucleus?

• stores DNA

• Controls cell division and growth

• Controls gene expression

Genome

All the DNA that an organism possesses

What are the three components of a nucleotide?

Phosphate group, sugar, nitrogenous baseW

What are the two components of a nucleoside?

Penrose sugar, nitrogenous base

Centromere

Constricted region of chromosome that stains less strongly; spindle microtubules attach here for mitosis

Telomere

specialized sequences at each end of an eukaryotic chromosome

Cytogenetics

The field of genetics that involves microscopic examination of chromosomes

How many pairs of chromosomes do the dog have?

39 pairsH

Ow many pairs of chromosomes do the cat have?

19 pairs

How many pairs of chromosomes do horses have?

32 pairs

Karyotype Rules

• P (short) on top and q (large) on bottom

• Largest to smallest chromosome