Work

Spatial distribution of blood-brain barrier membrane proteins is controlled by sorting motifs and physiological signals in vivo

Year: 2026

Type: article

Abstract: The blood-brain barrier (BBB), formed by brain endothelial cells (BECs), creates a safe and homeostatic environment for proper brain function. While BECs are extraordinarily thin, their luminal and abluminal plasma membranes face markedly different environments: the blood and brain parenchyma, respectively. How BBB membrane proteins are spatially distributed between these membranes and the factors regulating their localization are not clear. Here, we establish a method for measuring polarized protein sorting at the BBB in vivo. We characterize the distribution of transporters and receptors on the luminal and abluminal plasma membranes and identify protein-intrinsic motifs that control polarized sorting. Finally, we observe a change in membrane protein distribution that aligns with circadian rhythms, revealing an under-appreciated dimension of BBB dynamics. This method can be broadly used for evaluating membrane protein landscape changes during development and disease and for choosing optimal molecular targets for BBB-crossing therapeutics.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.118134

Authors: Joseph Amick, Shamika Bhandarkar, Douglas R. Wilcox, Solenn Boloker, Yi Daniel Lu, Chenghua Gu

Institutions: Howard Hughes Medical Institute, Harvard University, Brigham and Women's Hospital, Massachusetts General Hospital

Language: English

Topic: Barrier Structure and Function Studies

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620