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Updated: Jun 25, 2025

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
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Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin

Published on: July 14, 2017

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VAMP2 controls murine epidermal differentiation and carcinogenesis by regulation of nucleophagy

Han Liu1, Peihong Su1, Yuanyuan Li1

  • 1Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.

Developmental Cell
|May 29, 2024
PubMed

Insights

Vesicle-associated membrane protein 2 (VAMP2) and focal adhesion kinase family interacting protein of 200 kDa (FIP200) are crucial for skin cell differentiation and preventing skin cancer. Their loss impairs epidermal differentiation and promotes tumor development.

Area of Science:

  • Cell Biology
  • Dermatology
  • Molecular Biology

Background:

  • Epidermal differentiation is a complex process involving cell cycle exit, cornified envelope formation, and organelle/nuclear dissolution.
  • Disruptions in epidermal differentiation are linked to skin diseases, including skin cancers.
  • Understanding the molecular regulators of epidermal differentiation is vital for addressing skin pathologies.

Purpose of the Study:

  • To identify novel factors regulating murine epidermal stem/progenitor cell differentiation.
  • To investigate the role of vesicle-associated membrane protein 2 (VAMP2) in epidermal differentiation and skin carcinogenesis.
  • To elucidate the molecular mechanisms connecting VAMP2, FIP200, and epidermal differentiation.

Main Methods:

  • Genome-wide shRNA screening to identify key factors in skin differentiation.
  • In vivo studies involving gene deletion (VAMP2) to assess effects on skin structure and differentiation.
  • Quantitative proteomics to identify VAMP2-interacting proteins.
  • Analysis of VAMP2 and FIP200 roles in keratinocyte enucleation and epidermal differentiation.
  • Assessment of VAMP2 and FIP200 loss on cutaneous carcinogenesis models.

Main Results:

  • Vesicle-associated membrane protein 2 (VAMP2) was identified as a critical factor in skin differentiation.
  • VAMP2 deletion resulted in abnormal skin stratification and impaired enucleation in vivo.
  • Focal adhesion kinase family interacting protein of 200 kDa (FIP200), an autophagy protein, was identified as a VAMP2 binding partner.
  • Both VAMP2 and FIP200 are essential for keratinocyte enucleation and proper epidermal differentiation.
  • Loss of VAMP2 or FIP200 accelerated skin tumor formation in vivo.

Conclusions:

  • VAMP2 and FIP200 play critical, coordinated roles in murine epidermal differentiation, specifically in keratinocyte enucleation.
  • These proteins are important regulators of skin barrier formation and homeostasis.
  • VAMP2 and FIP200 act as tumor suppressors in the context of skin carcinogenesis, highlighting their significance in preventing skin cancers.
Keywords:
autophagydifferentiationepidermal progenitor cellsskinsquamous cell carcinoma

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