Figure 1.

Mutations in MYO5B cause MVID. (A) MYO5B mutations and conformations. MYO5B consists of a motor domain, a neck domain that can bind 6 calmodulins to increase rigidity, and a tail domain that can bind Rab proteins. The open active conformation of MYO5B allows for ATP driven transport along actin. In the proposed closed inactive MYO5B conformation, the head and tail domains directly interact, and the motor cannot translocate along actin. (B) Model of MYO5B trafficking at the apical surface of normal and MVID affected enterocytes. (Left) In normal enterocytes, MYO5B works to apically traffic transporters, enzymes, and brush boarder components. (Right) In MVID, transporters, enzymes, and brush boarder components are not apically localized, but CFTR is retained at the apical surface, suggesting that it is delivered independently of MYO5B. Figure created using Biorender. (C) Abnormal PAS staining and inclusion formation in MYO5B knockout mice. (i) PAS staining in wild-type mice showing normal PAS-positive brush border and gross morphology. (ii) PAS staining in MYO5B knockout mouse showing blunted microvilli and accumulation of PAS stain below the apical surface. (iii) Fracture transmission electron microscopy showing microvillus inclusions formed on the interior of knockout mouse enterocytes.