Junichi Takagi 교수

Among adhesion receptor families, integrins are particularly important in biological processes that require rapid modulation of adhesion and de-adhesion. Activation on a timescale of < 1 s of beta2 integrins on leukocytes and beta3 integrins on platelets enables deposition of these cells at sites of inflammation or vessel wall injury. Recent crystal, nuclear magnetic resonance (NMR), and electron microscope (EM) structures of integrins and their domains lead to a unifying mechanism of activation

SORLA/SORL1 is a unique neuronal sorting receptor for the amyloid precursor protein that has been causally implicated in both sporadic and autosomal dominant familial forms of Alzheimer's disease (AD). Brain concentrations of SORLA are inversely correlated with amyloid-β (Aβ) in mouse models and AD patients, suggesting that increasing expression of this receptor could be a therapeutic option for decreasing the amount of amyloidogenic products in affected individuals. We characterize a new mouse

Since the discovery of the RGD sequence motif as the essential cell attachment site in Fn (fibronectin), RGD-dependent ligand recognition by integrins has been the major focus of many integrin researches. Although many integrins recognize RGD-containing ligands, it is believed that residues outside the RGD motif provide specificity as well as high affinity for each integrin-ligand pair. These 'secondary' sites are generally assumed to interact directly with the alpha subunit of integrin, whereas

Integrin α₅β₁ is a major fibronectin receptor critical for cell migration. Upon complex formation, fibronectin and α₅β₁ undergo conformational changes. While this is key for cell-tissue connections, its mechanism is unknown. Here, we report cryo-electron microscopy structures of native human α₅β₁ with fibronectin to 3.1-angstrom resolution, and in its resting state to 4.6-angstrom resolution. The α₅β₁-fibrone

The affinity of the extracellular domain of integrins for ligand is regulated by conformational changes signaled from the cytoplasm. Alternative types of conformational movement in the ligand-binding headpiece have been proposed. In one study, electron micrograph image averages of the headpiece of integrin aV beta 3 show two different conformations. The open conformation of the headpiece is present when a ligand mimetic peptide is bound and differs from the closed conformation in the presence of

Integrins mediate signal transduction through interaction with multiple cellular or extracellular matrix ligands. Integrin alphavbeta3 recognizes fibrinogen, von Willebrand factor, and vitronectin, while alphavbeta1 does not. We studied the mechanisms for defining ligand specificity of these integrins by swapping the highly diverse sequences in the I domain-like structure of the beta1 and beta3 subunits. When the sequence CTSEQNC (residues 187-193) of beta1 is replaced with the corresponding CYD