Emerin self-assembly and nucleoskeletal coupling regulate nuclear envelope mechanics against stress
Anthony Fernandez1, Markville Bautista2, Liying Wu1
1Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089, USA.
Journal of Cell Science
|February 18, 2022
Summary
Emerin protein clusters at the nuclear envelope, adapting nuclear shape under mechanical stress. Mutations in emerin cause X-linked Emery-Dreifuss muscular dystrophy by disrupting these essential protein structures.
Area of Science:
- Cell Biology
- Biophysics
- Structural Biology
Background:
- Emerin is a nuclear envelope protein crucial for maintaining nuclear shape.
- Emerin dysfunction causes X-linked Emery-Dreifuss muscular dystrophy (EDMD).
- The molecular mechanisms underlying emerin's role in nuclear mechanics are not fully understood.
Purpose of the Study:
- To elucidate the nanoscale organization and molecular interactions of emerin at the nuclear envelope.
- To investigate how emerin contributes to nuclear shape adaptation under mechanical stress.
- To identify the structural defects in emerin that lead to EDMD.
Main Methods:
- Single-molecule tracking microscopy.
- Super-resolution microscopy.
- Analysis of emerin's interactions with lamin A/C, LINC complex, nuclear actin, and BAF.
Main Results:
- Emerin forms oligomeric nanoclusters stabilized by lamin A/C and the SUN1-LINC complex.
- Nuclear actin and BAF modulate emerin's mobility and oligomerization.
- Emerin's oligomeric state changes in response to mechanical stress, driving nuclear shape adaptation.
- EDMD emerin mutants exhibit aberrant nuclear envelope deformations due to failed oligomer formation.
Conclusions:
- Emerin is central to nuclear mechanotransduction and shape remodeling.
- Proper emerin oligomerization, stabilized by lamin A/C and LINC, is vital for nuclear integrity.
- Defective emerin oligomerization underlies the pathogenesis of EDMD.
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