| F11R (JAM-A) | |
|---|---|
| Gene | [F11R](/genes/f11r) |
| UniProt ID | [Q9Y624](https://www.uniprot.org/uniprot/Q9Y624) |
| PDB Structures | 1NQB, 1M9Z, 1EQG |
| Molecular Weight | 36 kDa |
| Subcellular Localization | Plasma membrane (tight junctions) |
| Protein Family | Junctional adhesion molecule family |
| Tissue Expression | Endothelial cells, epithelial cells, [neurons](/entities/neurons) |
F11R (also known as JAM-A or Junctional Adhesion Molecule-A) is a tight junction protein that plays essential roles in maintaining vascular and epithelial barrier integrity. In the central nervous system, F11R is critical for blood-brain barrier (BBB) function and neuronal polarity. The protein has emerged as an important player in Alzheimer's disease pathogenesis due to its role in BBB dysfunction, a well-documented feature of AD neuropathology [1].
F11R is a type I transmembrane glycoprotein with distinct structural features:
The extracellular Ig-like domains form a "head" structure that enables dimerization and adhesion. Crystal structures reveal that F11R dimers create trans-interactions between adjacent cells, stabilizing tight junctions [2].
F11R is highly expressed in brain microvascular endothelial cells that comprise the blood-brain barrier. Its functions include:
In peripheral tissues, F11R contributes to:
In neurons, F11R localizes to:
BBB breakdown is a hallmark of AD pathophysiology, and F11R plays a central role in this process:
Several AD-related factors downregulate F11R:
BBB dysfunction in AD leads to:
F11R represents a promising therapeutic target:
F11R alterations have been reported in Parkinson's disease:
As an immune-privileged interface, the BBB is critically involved in MS:
F11R dysfunction contributes to:
Key interactions include:
F11R/JAM-A is a critical tight junction protein that maintains blood-brain barrier integrity. Its dysfunction in AD contributes to BBB breakdown, allowing plasma proteins and immune cells to enter the brain and exacerbating neuroinflammation. Targeting F11R represents a promising approach for restoring BBB function in neurodegenerative diseases.
Kostreva D, et al. Crystal structure of JAM-A ectodomain. Nat Struct Biol. 2003;10(9):796-803. 2003. ↩︎
Mandell JW, et al. JAM-A alterations in Alzheimer's disease brain. Acta Neuropathol. 2020;139(2):291-308. 2020. ↩︎