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Review
. 2022 Sep 12:10:989217.
doi: 10.3389/fcell.2022.989217. eCollection 2022.

The LEM-ESCRT toolkit: Repair and maintenance of the nucleus

Sapan Borah  1 , Karthigeyan Dhanasekaran  2 , Santosh Kumar  3
Affiliations
Review

The LEM-ESCRT toolkit: Repair and maintenance of the nucleus

Sapan Borah et al. Front Cell Dev Biol. .

Abstract

The eukaryotic genome is enclosed in a nuclear envelope that protects it from potentially damaging cellular activities and physically segregates transcription and translation.Transport across the NE is highly regulated and occurs primarily via the macromolecular nuclear pore complexes.Loss of nuclear compartmentalization due to defects in NPC function and NE integrity are tied to neurological and ageing disorders like Alzheimer's, viral pathogenesis, immune disorders, and cancer progression.Recent work implicates inner-nuclear membrane proteins of the conserved LEM domain family and the ESCRT machinery in NE reformation during cell division and NE repair upon rupture in migrating cancer cells, and generating seals over defective NPCs. In this review, we discuss the recent in-roads made into defining the molecular mechanisms and biochemical networks engaged by LEM and many other integral inner nuclear membrane proteins to preserve the nuclear barrier.

Keywords: ESCRT; NEBD; NPC; NUP; lem; nuclear envelope.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) General structure of the NPC (B) A schematic of NPC-related diseases.
FIGURE 2
FIGURE 2
Schematic of the nuclear envelope listing key questions addressed in this review.
FIGURE 3
FIGURE 3
Proposed model of NPC surveillance by the LEM protein Heh2. The C-terminus winged-helix domain of Heh2 cannot bind to structurally compromised NPC and might act as a sensor of the NPC assembly state (Borah et al., 2021).
FIGURE 4
FIGURE 4
Rearrangement of the nuclear components at the onset of cell division. The left panel represents interphase NE status in a cell, while the right panel shows the status during NEBD onset during prophase in open mitosis.
FIGURE 5
FIGURE 5
Loss of NE integrity beyond mitosis.
See this image and copyright information in PMC

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