Diversity of clathrin function: new tricks for an old protein

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Clathrin is a fundamental vesicle coat protein essential for membrane cargo sorting and lipid modifier recruitment.
• Decades of research have elucidated clathrin's role in receptor-mediated endocytosis, particularly yolk protein uptake.
• This review synthesizes current knowledge on clathrin's structure, biochemistry, and protein interactions.

Purpose of the Study:

• To review the diverse functions of clathrin beyond conventional receptor-mediated endocytosis.
• To highlight the distinct roles of human clathrin isoforms, CHC17 and CHC22.
• To establish the relevance of clathrin function to human health and disease.

Main Methods:

• Review of existing literature on clathrin biochemistry, structure, and function.
• Analysis of clathrin heavy and light chain subunit properties.
• Examination of clathrin light chain interactions with Hip proteins and actin.

Main Results:

• Clathrin exhibits diverse functions, including intracellular sorting, mitosis regulation, and specialized roles in glucose transport (CHC22).
• Clathrin light chain interaction with Hip proteins reveals a novel actin-organizing role for CHC17 clathrin during bacterial infection.
• Distinct human clathrin isoforms (CHC17 and CHC22) possess specialized functions impacting cellular processes and human metabolism.

Conclusions:

• Clathrin's functions extend significantly beyond its established role in endocytosis.
• The specialized functions of clathrin isoforms, particularly CHC22 in glucose metabolism and CHC17 in actin organization, underscore its broad relevance.
• Understanding clathrin's diverse roles is crucial for comprehending its implications in human health and disease.