EHBP1L1, an apicobasal polarity regulator, is critical for nuclear polarization during enucleation of erythroblasts

Abstract

Cell polarity, the asymmetric distribution of proteins and organelles, is permanently or transiently established in various cell types and plays an important role in many physiological events. EH domain-binding protein 1 like 1 (EHBP1L1) is an adaptor protein that is localized on recycling endosomes and regulates apical-directed transport in polarized epithelial cells. However, the role of EHBP1L1 in non-epithelial cells remains unknown. In this study, Ehbp1l1-/- mice showed impaired erythroblast enucleation. Further analyses showed that nuclear polarization prior to enucleation was impaired in Ehbp1l1-/- erythroblasts. It was also revealed that EHBP1L1 interactors Rab10, Bin1, and dynamin were involved in erythroblast enucleation. In addition, Ehbp1l1-/- erythrocytes exhibited stomatocytic morphology and dehydration. These defects in erythroid cells culminated in early postnatal anemic lethality in Ehbp1l1-/- mice. Moreover, we found the mislocalization of nuclei and mitochondria in the skeletal muscle cells of Ehbp1l1-/- mice, as observed in patients with centronuclear myopathy with genetic mutations in Bin1 or dynamin 2. Taken together, our findings indicate that the Rab8/10-EHBP1L1-Bin1-dynamin axis plays an important role in multiple cell polarity systems in epithelial and non-epithelial cells.

Comparative genomics of macaques and integrated insights into genetic variation and population history

“…Similarly, a fixed 72 bp insertion in EHBP1L1 in MFA, with respect to MMU and other apes, led to a 24 amino acid insertion. EHBP1L1 is involved in apicobasal polarity and cilia length regulation 85,86 (Figure 3m). To further validate our findings, we confirmed these genetic variants using Iso-Seq data (Supplementary Figure 30).…”

“…The PLA2G3 gene encodes an enzyme involved in lipid metabolism, and its knockout in mice leads to defects in sperm maturation and fertility 87 . EHBP1L1 is involved in the Rab8/10-EHBP1L1-Bin1-dynamin signal transduction pathway, which is essential for maintaining cell polarity 85,86 . Loss of EHBP1L1 results in lethal anemia in mice 85 .…”

“…EHBP1L1 is involved in the Rab8/10-EHBP1L1-Bin1-dynamin signal transduction pathway, which is essential for maintaining cell polarity 85,86 . Loss of EHBP1L1 results in lethal anemia in mice 85 .…”