Envelope proteins and their potential roles in EDMD physiopathology (WP4535)

Homo sapiens

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Schematic model of the nuclear envelope proteins and their potential roles in Emery-Dreyfuss muscular dystrophy (EDMD) physiopathology. Nuclear lamins form a meshwork. It interacts with proteins of the nuclear envelope, i.e., EMD, LBR, TMPO, SUN, and MAN1, and with several transcription factors. Through nesprin proteins, lamins interact with actin microfilaments, microtubules, and cytoplasmic intermediate filaments, connecting the nuclear lamina to the extracellular matrix. MKL1 translocates into the nucleus and together with SRF induces gene expression. In addition, EMD facilitates polymerization of nuclear actin, reducing the nuclear export of MKL1 to the cytoplasm. In EDMD cells, emerin mislocalizes and is unable to modulate nuclear actin polymerization. G-actin binds to MKL1 and it is exported from the nucleus, impairing gene expression. YAP and TAZ are key transcription factors for cell proliferation. YAP/TAZ activation causes their nuclear accumulation, promoting cell proliferation, and inhibiting differentiation. Nuclear localization of YAP/TAZ is increased in patient myoblasts with LMNA mutations.

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Authors

Laurent Winckers , Marvin Martens , Alex Pico , Friederike Ehrhart , Eric Weitz , Kristina Hanspers , and Daniela Digles

Activity

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Organisms

Homo sapiens

Communities

Rare Diseases

Annotations

Disease Ontology

Emery-Dreifuss muscular dystrophy

Pathway Ontology

disease pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
ADCY1 GeneProduct ncbigene:107 A/C
ADCY2 GeneProduct ncbigene:108 A/C
ADCY3 GeneProduct ncbigene:109 A/C
ADCY4 GeneProduct ncbigene:196883 A/C
ADCY5 GeneProduct ncbigene:111 A/C
ADCY6 GeneProduct ncbigene:112 A/C
ADCY7 GeneProduct ncbigene:113 A/C
ADCY8 GeneProduct ncbigene:114 A/C
ADCY9 GeneProduct ncbigene:115 A/C
SYNE1 GeneProduct ncbigene:23345 nesprin1/2
TGFB1 GeneProduct ncbigene:7040 TGF-B
TGFB2 GeneProduct ncbigene:7042 TGF-B
TAZ GeneProduct ncbigene:25937 YAP/TAZ
YY1AP1 GeneProduct ncbigene:55249 YAP/TAZ
TMPO GeneProduct ncbigene:7112
SYNE4 GeneProduct ncbigene:163183 nesprin4
PLEC GeneProduct ncbigene:5339
MAP2K2 GeneProduct ncbigene:5605 MEK
Smad3 GeneProduct ncbigene:4088
Cofilin-1 GeneProduct ncbigene:1072
SYNE3 GeneProduct ncbigene:161176 nesprin3
HRAS GeneProduct ncbigene:3265 Ras
SOS2 GeneProduct ncbigene:6655
Grb2 GeneProduct ncbigene:2885
SUN GeneProduct ncbigene:23353
NRAS GeneProduct ncbigene:4893 Ras
MAP2K1 GeneProduct ncbigene:5604 MEK
Smad2 GeneProduct ncbigene:4087
MAPK1 GeneProduct ncbigene:5594 ERK
EMD GeneProduct ncbigene:2010
CTGF GeneProduct ncbigene:1490 CTGF/CCN2
BANF1 GeneProduct ncbigene:8815 BAF
MAPK3 GeneProduct ncbigene:5595 ERK
SYNE2 GeneProduct ncbigene:23224 nesprin1/2
Smad4 GeneProduct ncbigene:4089
TMEM43 GeneProduct ncbigene:79188 LUMA
ADCY10 GeneProduct ncbigene:55811 A/C
MAP3K9 GeneProduct ncbigene:4293 MLK1
LEMD3 GeneProduct ncbigene:23592 MAN-1
SRF GeneProduct ncbigene:6722 SRF
KIF5B GeneProduct ncbigene:3799 Kif5B
KRAS GeneProduct ncbigene:3845 Ras
SOS1 GeneProduct ncbigene:6654
LBR GeneProduct ncbigene:3930 LBR
RhoA GeneProduct ncbigene:387
TGFB3 GeneProduct ncbigene:7043 TGF-B

References

  1. The Pathogenesis and Therapies of Striated Muscle Laminopathies. Brull A, Morales Rodriguez B, Bonne G, Muchir A, Bertrand AT. Front Physiol. 2018 Oct 30;9:1533. PubMed Europe PMC Scholia