Article

The LDL receptor-related protein (LRP) family: an old family of proteins with new physiological functions.

Universität Freiburg, Medizinische Klinik II/Zentrum für Neurowissenschaften, Freiburg, Germany.
Annals of Medicine (Impact Factor: 4.73). 02/2007; 39(3):219-28. DOI: 10.1080/07853890701214881
Source: PubMed

ABSTRACT The low-density lipoprotein (LDL) receptor is the founding member of a family of seven structurally closely related transmembrane proteins (LRP1, LRP1b, megalin/LRP2, LDL receptor, very low-density lipoprotein receptor, MEGF7/LRP4, LRP8/apolipoprotein E receptor2). These proteins participate in a wide range of physiological processes, including the regulation of lipid metabolism, protection against atherosclerosis, neurodevelopment, and transport of nutrients and vitamins. While currently available data suggest that the role of the LDL receptor is limited to the regulation of cholesterol homeostasis by receptor-mediated endocytosis of lipoprotein particles, there is growing experimental evidence that the other members of the gene family have additional physiological functions as signal transducers. In this review, we focus on the latest discovered functions of two major members of this family, LRP1 and megalin/LRP2, and on the newly elucidated physiological role of a third member of the family, MEGF7/LRP4, which can also function as a modulator of diverse signaling pathways during development.

2 Bookmarks
 · 
319 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Kawasaki disease (KD) is an acute and systemic vasculitis. Its complications in coronary artery aneurysms (CAA) make KD one of the leading causes of acquired cardiovascular diseases in childhood. Low density lipoprotein receptor-related protein 1B (LRP1B) is abundantly expressed in the medial layer of coronary arteries and involved in endothelium inflammations. Purpose: We aimed to identify the role of LRP1B in CAA formation during KD progression. Methods: we investigated genetic variations in LRP1B in a Taiwanese cohort of 258 KD patients (83 with CAA and 175 without CAA complications). We used univariate and multivariate regression analyses to identify the associations between LRP1B genetic variations and KD patients. Results: CAA formation in KD was significantly associated with the LRP1B (rs6707826) genetic variant (p = 0.007). By using multivariate regression analysis, significant correlations were observed between KD with CAA complications and the presence of the TT+TG genotypes for the LRP1B rs6707826 single-nucleotide polymorphism (full model: odds ratio = 2.82; 95% CI = 1.33-5.78). Conclusion: Our results suggest that genetic polymorphism of LRP1B gene may be used as a genetic marker for the diagnosis and prognosis of the CAA formation in KD and contribute to genetic profiling studies for personalized medicine.
    BioMedicine. 06/2014; 4:10.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cell surface-associated proteolysis mediated by plasmin (PLA) is an essential feature of wound healing, angiogenesis and cell invasion, processes that are dysregulated in cancer development, progression and systemic spread. The generation of PLA, initiated by the binding of its precursor plasminogen (PLG) to the cell surface, is regulated by an array of activators, inhibitors and receptors. In this review, we will highlight the importance of the best-characterized components of the PLG/PLA cascade in the pathogenesis of cancer focusing on the role of the cell surface-PLG receptors (PLG-R). PLG-R overexpression has been associated with poor prognosis of cancer patients and resistance to chemotherapy. We will also discuss recent findings on the molecular mechanisms regulating cell surface expression and distribution of PLG-R.
    International Journal of Molecular Sciences 11/2014; 15(11):21229-21252. · 2.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transporte del β-amilode a través de las barreras cerebrales y su posible implicación en el desarrollo de la enfermedad de Alzheimer. Summary β-amyloid transport through the brain barrier and its possible role in the development of Alzheimer's disease. The clearance of β-amyloid, through its accurate metabolism in the brain, is essential to prevent neurodegenerative diseases such as Alzheimer's disease (AD). Thus, it is postulated that a defective β-amyloid clearance by brain barriers, both the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (BCSFB) barrier, could be an important factor in the onset and development of AD. The β-amyloid (βA) located in the interstitial fluid (IF) can pass to the blood through the BBB or passively move to LCR where βA is kidnapped by the choroid plexus from CSF into the blood. It is proposed that the cause of most cases of sporadic AD (late onset), may be due to improper clearance of β-amyloid in the brain, so that dementia in AD could be associated with the brain barrier disorder, leading to the accumulation of β-amyloid on blood vessels, the brain parenchyma , and extracellular and intraneuronal form deposits. Key words β-amyloid, brain barriers, Alzheimer disease.
    Majorensis. 01/2014; 10(1):7-15.

Full-text

Download
69 Downloads
Available from
May 20, 2014