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A Ticket to Nowhere

Lysosomal Storage Disorders

By Rachel A. Hirst, Tracy R. Rosebrock

A Ticket to Nowhere


 

Abstract

This directed case study connects the physiological symptoms and genetic mutations associated with mucolipidosis II, a lysosomal storage disorder (LSD), to the mislocalization of certain lysosomal hydrolases caused by the lack of an important post-translational modification on these enzymes. Students follow the story of “Ana Sophia” through the perspective of Ana’s pediatrician. At Ana’s six-month well visit, Ana presents with symptoms consistent with an LSD including reduced mobility. Students follow the pediatrician’s process of confirming that a lysosomal storage disorder is the cause of Ana’s symptoms and identify her specific disorder. The case is designed for undergraduate students who have completed introductory biology courses and have foundational knowledge of protein structure, enzyme function, post-translational modifications, the endomembrane system, and the structure and function of the lysosome. Students review important concepts in cellular biology and then apply those concepts using critical and divergent thinking to explain disease symptomatology, generate hypotheses, interpret test results, conduct thought experiments, and synthesize newly acquired knowledge with additional research in a final written homework assignment.

   

Date Posted

02/06/2023

Overview

Objectives

  • Illustrate the journey of lysosomal hydrolases through the endomembrane system.
  • Explain the role of post-translational modification to direct the correct localization of lysosomal hydrolases to lysosomes.
  • Describe the function and requirements of lysosomal hydrolases in the lysosome.
  • Explain the role of a chondrocyte cell in generating cartilage tissue.
  • Define lysosomal storage disorders.
  • Compare and contrast quantification of intracellular and extracellular hydrolase activity.
  • Form conclusions from data visualized in a bar graph.
  • Design hypotheses to explain defects in lysosomal hydrolase trafficking.
  • Explain how a variant in GNPTAB results in the mis-localization of multiple lysosomal hydrolases and, ultimately, mucolipidosis II disease.

Keywords

Lysosomal storage disorder; LSD; protein structure; post-translational modification; glycosylation; protein trafficking; hydrolase; endomembrane; lysosome; chondrocyte; mucolipidosis

  

Subject Headings

Biology (General)
Cell Biology

EDUCATIONAL LEVEL

Undergraduate lower division, Undergraduate upper division

  

FORMAT

PDF, PPTX

   

TOPICAL AREAS

N/A

   

LANGUAGE

English

   

TYPE/METHODS

Directed, Discussion, Interrupted

 

 

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