Dispatched uses Na⁺ flux to power release of lipid-modified Hedgehog.

ABSTRACT: The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters^1,2 and to H⁺-driven transporters of the RND family^3,4, enables tissue-patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly -localized sites of embryonic expression^5-10. Here we determine a cryo-electron microscopy structure of the mouse protein Dispatched homologue 1 (DISP1), revealing three Na⁺ ions coordinated within a channel that traverses its transmembrane domain. We find that the rate of Hedgehog export is dependent on the Na⁺ gradient across the plasma membrane. The transmembrane channel and Na⁺ binding are disrupted in DISP1-NNN, a variant with asparagine substitutions for three intram

SUBMITTER: Wang Q 

PROVIDER: S-EPMC8785653 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature