U01.01.024 Cell trafficking

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Learning Objectives

  • Describe the role of the Golgi apparatus as the cellular distribution center.
  • Identify the three main vesicular trafficking proteins (COPI, COPII, Clathrin).
  • Explain the importance of Mannose-6-phosphate for lysosomal targeting.
  • Correlate Golgi trafficking defects with I-cell disease.

1. The Golgi Apparatus: Posttranslational Processing

The Golgi modifies, sorts, and packages proteins and lipids from the ER. Key modifications include:

  • N-oligosaccharide modification: Occurs on Asparagine.
  • O-oligosaccharide addition: Occurs on Serine and Threonine.
  • Lysosomal Targeting: Addition of Mannose-6-phosphate (M6P) to proteins. This “zip code” ensures enzymes are delivered to lysosomes rather than secreted.

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2. Vesicular Trafficking Proteins

Specific coat proteins determine the direction of vesicle movement between the ER, Golgi, and plasma membrane.

Protein Direction Mnemonic
COPII ER → cis-Golgi (Anterograde) Two (COPII) steps forward.
COPI cis-Golgi → ER (Retrograde) or Golgi → Golgi One (COPI) step back.
Clathrin trans-Golgi → Lysosomes; Plasma membrane → Endosomes Used for receptor-mediated endocytosis (e.g., LDL).

3. Signal Recognition Particle (SRP)

The SRP is a cytosolic ribonucleoprotein that acts as a traffic controller. It recognizes the signal sequence on a growing polypeptide and traffics the ribosome complex from the cytosol to the RER.

  • Dysfunction: If SRP is absent, proteins intended for secretion or organelles will accumulate in the cytosol.

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4. Clinical Correlation: I-Cell Disease

I-cell disease (Mucolipidosis type II) is a severe autosomal recessive lysosomal storage disorder.

  • Defect: Deficiency in N-acetylglucosaminyl-1-phosphotransferase.
  • Pathophysiology: Failure of the Golgi to phosphorylate mannose residues → \downarrow Mannose-6-phosphate → Enzymes are secreted extracellularly instead of being delivered to lysosomes.
  • Result: Lysosomes lack digestive enzymes; cellular debris builds up (Inclusion bodies).
  • Presentation: Coarse facial features, gingival hyperplasia, corneal clouding, claw hand, and \uparrow plasma levels of lysosomal enzymes.

 

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