Supplementary Figure 4: Interaction of nuclear pore complex (NPC) proteins NUP93 and NUP205 with SMAD, importin 7 (IPO7) and exportin 5 (XPO5) showing the positions of the mutations that abrogate interactions.
From: Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome
(a) Subcomplexes of the NPC are depicted and labeled in different colors. (b) Inset from a. NUP93 and NUP155 are tethered to the nuclear membrane by NUP53. The three-dimensional structure of NUP93 is shown in relation to the likely positions of interaction with NUP205, IPO7 or SMADs. The positions of the NUP93 and NUP205 mutations that abrogate the interaction and were found in individuals with SRNS are marked by yellow lightning signs. (c) BMP7 binding to its receptor causes phosphorylation of SMAD1/5/8, resulting in dissociation from the receptor and binding to SMAD4. The SMAD4/1/5/8 complex interacts with importin 7, enabling the SMAD complex to enter the nucleus through the NPC via NUP93 interaction, bind to cognate DNA sites and initiate transcription of SMAD downstream targets. (d) XPO5 binds to SMAD4 for nuclear export. Deletion of the nuclear export signal of SMAD4 abrogates interaction with XPO5.
