The Golgi apparatus, Perixsome, Lysosome

Golgi apparatus structure

• several membrane-covered stacked, flattened sacs (or cisternae)

• the sacs are disk-like and often slightly curved (convex and concave surfaces )

• Vesicles go from cis to trans

Golgi apparatus function

• sorting system for proteins coming from the RER

• Modifies the proteins by glycosylation

• activation of peptides by proteolysis or phosphorylation

• synthesis of glycosaminoglycans and mucin

• Selection enzymes for lysosome

Destination of proteins synthesize in the RER and passing through the GOLGI

• come back to RER

• remain in golgi

• go to lysosomes

• undergo exocytosis

Destination of proteins from the golgi

• proteins found in the lumen of Golgi that need to go to RER - have a sequence of amino acid: KDEL - to be recognized by KDEL receptors

• Proteins that continue in Golgi - lack signal peptide KDEL - may present other signals to bind to membranes sites

• Proteins to be delivered to lysosomes - have specific marker - 6 phosphate mannose

Content leaving golgi can undergo?

• constitutive secretion

• regulated secretion

Constiutive secretion

• vesicles coated by coating proteins (COPs)

• not dependent on specific stimulatin

• secretion products - immediately secreted

• continuous process

Regulated secretion

• vesicle coated clathrin proteins - controlled by specific stimulation

• Proteins to be secreted are stored into vesicles that accumulate close to plasma membrane fuse with the membrane after specific extraceullular stimulation

Vesicle traficking

ENDOCYTOSIS (IN)

• the vesicle originates from the plasma membrane and internalizes extracellular material

EXOCYTOSIS (OUT)

he vesicle originates intra-cellularly and fuses with the plasma membrane, thus releasing its content in the extracellular space

GEMMATION

the vesicle originates from a cell membrane and the whole vesicle (with its content) goes in the extracellular environment (ex: apocrine secretion).

Coating functiono

• coating of proteins - favours bending of the membrane during the formation of vesicle

• allows selection of components that have to be inserted and transported into a vesicle

• Direction and destination - transmembrane protein v-SNARE on vesicles recognizes sequence t-SNARE on the target memrbane

COPs coating

• coated by COP 2- move from RER to Golgi

• coated by COP 1 - move from Golgi to RER

• Veiscles coated by clathrin - move from Golgi to plasma membrane or to endosomes

Types of endocytosis

• receptor-mediated endocytosis - after the molecules binded to specific membrane receptors

• pinocytosis - very tiny soluble molecules

• phagocytosis - particular molecules, bacteria

• autophagy - specific type of endocytosis

Clathrin-mediated endocytosis process

1. Extracellular ligands - bound to cell-surface receptors associated with the adaptor protein

2. bind to clathrin - forms a cage-like pit from the plasma membrane

3. As the coat grows - the vesicle pinches off - GTPase protein DYNamin forms a spiral collar around the base of vesicle

4. Following internalization - clathrin coat disassembles

5. Vesicel fuses with other membranes

6. In acidic early endosome - ligands are released from receptors - they are sorted away and go to the membrane

7. Internal vesicles will go to lysosomes

example: Low-Density lipoproteins receptors

Phagocytosis

• phagocytes - come from blood - able to destroy bacteria, viruses, damaged cells or dea

  PHASES

  1. Recognition and adsorption of the particle to be ingested

  2. Internalization of the particle - digestion in lysosomes

Lysosomes

• contain more than 50 lytic enzymes - break down waste material (proteins, nucleic acid, lipids, carbs)

• Protein of lysosomes - made in RER and tagged with mannose-6-phosphate

• interlinked with - phagocytosis, endocytosis, autophagy

• Active hydrolases

  • active at ph t

  • inactive if released in the cystol - pH 7.2

• Storage of melanin - in form of melanosomes

Lysosomal storage diseases

• group of diseases - abnormal accumulation of substances inside lysosomes

• cause - defects in lysosomal enzymes - required for metabolism of moleculess

• Examples: Tay-Sachs disease, Gaucher disease, Niemann-Pick disease, Hunter syndrome

• Children are affected: developmental delay, defects in many organs, movement disorders, dementia, early death.

PEROXISOMES

Heterogeneous group of membrane-bound organelles containing several enzymes acting in different metabolic activities

Originates from the rer

Features

• enzyme catalase - 40% of all enzymes - transorms H202 in water and O2

• variable shape

• number

• enzymes - fatty acid and amino acid oxidation - production of H202

• detoxification of dangerous substances penetrated into the organism

• removal of free radicals and reactive oxygen species (ROS), such as the superoxide radical, the hydroxyl radicals (OH-) that may damage cell DNA and proteins

Peroxisomes and CNS

Oligodendrocytes (type of Peroxisomes) - role in axonal integrity

Demadge of peroxisomes - axonal loss and demyelination

Formation of Perxomes

• come from RER

• Microvesicles contain peroxisome proteins - originate from rer

• fuse to form peroxisomes