Table 1. The role(s) of LEM domain, ESCRT, and other select proteins at the nuclear envelope.
Abbreviations: BAF, Barrier-to-Autointegration Factor; Ce, Caenorhabditis elegans; CHMP/Chm/Cmp, Charged Multivesicular Body Protein; CNEP-1, CTD Nuclear Envelope Phosphatase 1 Homolog; Elo, Elongation Of Fatty Acids Protein; ESCRT, Endosomal Sorting Complexes Required for Transport; Heh, helix-extension-helix; Hs, Homo sapiens; INM, inner nuclear membrane; LEM, LAP2, Emerin, MAN1; NPC, nuclear pore complex; Nur, Nuclear rim protein; Sj, Schizosaccharomyces japonicus; Sc, Saccharomyces cerevisiae; Sp, Schizosaccharomyces pombe; Vps, Vacuolar protein sorting; WH, winged helix; Xpo1, Exportin 1
| Protein | Species | Role(s) at nuclear envelope related to nuclear envelope surveillance/repair and post-mitotic reassembly |
|---|---|---|
| LEM-domain proteins | ||
| LEM2 | Sc (Hehl/Srcl) | – Required to recruit Chm7 to nuclear envelope upon genetic perturbation of NPC assembly [16] |
| – Cytosolic exposure of WH domain is sufficient to recruit and activate Chm7 at ER membranes [18] | ||
| Sp (Heh1/Lem2) | – Required for maintaining nuclear-cytoplasmic compartmentalization [69] | |
| – Helps control nucleus size, possibly by regulating membrane flow [68] | ||
| Sj | – Required for efficient nuclear envelope reformation after mitosis [70,71] | |
| Ce (LEM-2) | – Recruited to sites of nuclear rupture with ESCRT machinery [27] | |
| Hs | – Required for efficient nuclear envelope formation after mitosis, recruits CHMP7 [21] | |
| – Recruited to nuclear envelope ruptures by BAF; simultaneous deletion of LEM2, Emerin, and Ankle2 inhibits repair [28] | ||
| – WH domain forms co-polymer with CHMP7 [39] | ||
| Ankle2/LEM4 | Ce (LEM-4L) | – Required for nuclear envelope reassembly [72] |
| Hs | – Recruited to nuclear envelope ruptures by BAF; supports repair with LEM2 and Emerin [28] | |
| Emerin | Hs | – Recruited to nuclear envelope ruptures by BAF; supports repair with LEM2 and Ankle2 [28] |
| MAN1 | Sc (Heh2) | – N-terminal LEM-containing domain directly binds to Chm7 and Snf7 [16] |
| Sj | – Required for efficient disassembly and reformation of the nuclear envelope after mitosis [73] | |
| ESCRTs | ||
| CHMP7 | Sc (Chm7) | – Recruited to nuclear envelope upon perturbation of NPC assembly [16] |
| – Required to maintain nuclear envelope integrity in the context of nuclear envelope herniations [18] | ||
| – Exported from the nucleus by Crm1/Xpo1 [18] | ||
| – Hyperactivation by binding to Heh1 causes INM remodeling with extensions into the nucleus [18] | ||
| Sp (Cmp7) | – Acts to remodel nuclear envelope, suppressed by Vps4 [21] | |
| Sj (Cmp7) | – Required for efficient nuclear envelope reformation after mitosis; may play a role in releasing Lem2 from heterochromatin [71] | |
| Hs | – Directly interacts with membranes [22]; forms a co-polymer with LEM2 [39] | |
| – Required for efficient nuclear envelope reformation after mitosis [21,24] and for repair following mechanical disruption [25] | ||
| – Maintains stability of intact micronuclei [29]; hyperactivation drives membrane deformation and correlates with DNA damage [29,33] | ||
| – Exported from the nucleus by CRM1/XPO1 [33] | ||
| CHMP4A-C | Sc (Snf7) | – Required for recruitment of Vps4 to sites of Chm7 activation [18] |
| Sj (Vps32) | – Required for efficient nuclear envelope reformation after mitosis; may play a role in releasing Lem2 from heterochromatin [71] | |
| Ce (Vps32) | – Recruited to sites of nuclear rupture with LEM-2 [27] | |
| Hs | – Required for efficient nuclear envelope reformation after mitosis [23,24] and for repair following mechanical disruption [25,26] | |
| – Recruited to forming micronuclei [29,51] | ||
| CHMP1A,B | Sc (Did2) | – Required for recruitment of Vps4 to sites of Chm7 activation [18] |
| CHMP2A,B | Sc (Vps2) | – Required for recruitment of Vps4 to sites of Chm7 activation [18] |
| Hs | – Required for efficient nuclear envelope reformation after mitosis [23,24] and for repair following mechanical disruption [25] | |
| CHMP3 | Sc (Vps24) | – Required for recruitment of Vps4 to sites of Chm7 activation [18] |
| Hs | – Required for efficient nuclear envelope reformation after mitosis [23,24] and for repair following mechanical disruption [26] | |
| CHMP5 | Sc (Vps60) | – Required for recruitment of Vps4 to sites of Chm7 activation [18] |
| IST1 | Sc (Ist1) | – Required for recruitment of Vps4 to sites of Chm7 activation [18] |
| Hs | – Required for efficient nuclear envelope reformation after mitosis [24] | |
| VPS4 | Sc | – Functionally interacts with NPC biogenesis/quality control [16,17] |
| – Likely inhibits Chm7 hyperactivation [18] | ||
| Sp | – Likely inhibits Cmp7 hyperactivation [21] | |
| Sj | – Required for efficient nuclear envelope reformation after mitosis; may play a role in releasing Lem2 from heterochromatin [71] | |
| Hs | – Required for efficient nuclear envelope reformation after mitosis [23,24] and for repair following mechanical disruption [25] | |
| – Inhibits CHMP7 hyperactivation, likely resolves filaments to seal membranes [29] | ||
| Other | ||
| Nur1 | Sc | – Supports activation of Chm7, likely through Heh1 [18] |
| Sj | – Required for efficient nuclear envelope reformation after mitosis; may play a role in releasing Lem2 from heterochromatin [71] | |
| Spastin | Hs | – Required for efficient nuclear envelope reformation after mitosis, likely to sever microtubules [24] |
| CC2D1B | Hs | – Required for efficient nuclear envelope reformation after mitosis by orchestrating ESCRT recruitment [20] |
| BAF | Ce | – Required for efficient nuclear envelope reformation after mitosis [47] |
| Hs | – Required for efficient nuclear envelope reformation after mitosis [48] and for sealing large ruptures [28] | |
| Elo2 | Sp | – Produces long-chain fatty acids essential for nuclear envelope stability [53] |
| CNEP-1 | Ce | – Promotes production of phospholipids required for nuclear envelope reformation in meiosis [61] |