LRP2 mediates folate uptake in the developing neural tube

Kur, Esther; Mecklenburg, Nora; Cabrera, Robert M.; Willnow, Thomas E.; Hammes, Annette

doi:10.1242/jcs.140145

Cited by 45 publications

(60 citation statements)

References 44 publications

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“…On a FVB/N background, however, LRP2 null mice are viable with neural tube defects, and this receptor has previously been implicated in folate endocytosis in the developing neural tube. 53 However, peripheral blood and bone marrow hematopoietic stem and progenitor cell numbers were comparable in FVB/N wild-type and mutant adult mice at 6 to 9 months of age (supplemental Figure 10). A more detailed analysis of embryonic hematopoiesis in mutant mice on both C57Bl/6N and FVB/N backgrounds will be required to establish whether the numbers of emergent HSCs differ at various time points and the identity of any modifier genes in FVB/N that compensate for the loss of LRP2; these investigations are ongoing.…”

Section: Discussionmentioning

confidence: 94%

Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes

Nasrallah

Fast

Solaimani

et al. 2016

Blood

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Section: Discussionmentioning

confidence: 94%

Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes

Nasrallah

Fast

Solaimani

et al. 2016

Blood

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“…A recent study by Kur et al, [23] showed that low-density lipoprotein (LDL) receptor-related protein 2 (LRP2), mediates folate uptake in the developing neuroepithelium. LRP2-deficient neuroepithelial cells are unable to mediate the uptake of folate bound to soluble folate receptor 1 (sFOLR1).…”

Section: Reviewmentioning

confidence: 99%

“…Endocytosis of FRα is assisted by low-density lipoprotein (LDL) receptorrelated protein 2 (LRP2), a multifunctional cell-surface receptor expressed in the embryonic neuroepithelium [23] as well as by protein kinase Cα [24].…”

Section: Introductionmentioning

confidence: 99%

Novel functions of folate receptor alpha in CNS development and diseases

Mayanil¹,

Siddiqui²,

Tomita³

2014

Neurosci Discov

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Abstract(Folate receptor alpha), a GPI-anchored protein is critical for embryonic development. Disruption of both FRα alleles in mice results in pups with a range of malformations and is lethal to the embryos at the time of neural tube closure. Recent body of evidences emphasizes its role in neural tube defects, cerebral folate deficiency, autism and autism spectrum disorders. Circulating autoantibodies against FRα and cerebral folate deficiency appear to play a crucial role in the cause and pathogenesis of a particular subgroup of autism spectrum disorders with co-existing neurological deficits. Since FRα is known to be over-expressed in cancer cells, it has found a novel theranostic role in cancer diagnosis and treatment by using FA-conjugated imaging agents as diagnostic tools and FA-conjugated nanotherapeutics and immunotherapy for cancer. This review highlights some recent advances and novel roles of FRα other than it being just a folate transporter.

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“…The components of this transcytosis system are LRP2, AMN, CUBN, ARH, Dab2, GIPC, NHE3, ClC5, FcRn and NaPi-IIa, which mediate the reuptake of B complex vitamins, including folic acid among other molecules [3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…While mutations in AMN and CUB occur with megaloblastic anemia plus albuminuria. CUBallelic variants are related to the progression of renal damage and ARH variations are associated with hypercholesterolemia [3][4][5][6][7][8][9][10]. NHE3 mutations show association with congenital sodium diarrhea, whereas ClC5 gene is related to renal failure or Dent disease.…”

Section: Introductionmentioning

confidence: 99%

Exploration of gene variations in the transcytosis system as a policy proposal for the personalized therapy in type 2 diabetes mellitus

Flores-Alvarado¹,

Villafán-Bernal²,

Cabrera-Pivaral³

et al. 2017

J Med Therap

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The gene system of transcytosis, integrated by LRP2, AMN, CUBN, ARH, AMN and CUBN, might be important for the treatment and monitoring of chronic complications of diabetics, as well as for drug interactions, since they mediate the reuptake of vitamins such as B complex, folic acid and lipoproteins, which are closely related to the progression of diabetes. That is why polymorphisms in those genes could be targets of personalized medicine, to improve the quality of health care. It is important for both the clinical researcher and physician to explore new personalized treatment options for better care of the diabetic patient. The search for genetic or genomic markers in order to predict complications of disease, progression as well as to evaluate the therapeutic response to drugs and the presentation of adverse effects is an area to be explored, considering the high costs that represent the attention of diabetics to hospitals from the public sector. Other reasons are that type 2 diabetes mellitus (T2D) patients develop complications related with the progression of the disease, as well as, adverse and side effects resulting from drug interactions [1,2]. T2D commonly presents deficiency of vitamin B complex, associated with the long-term consumption of metformin. The consequences of this deficiency are increased cardiovascular risk, renal damage and higher risk of peripheral neuropathy and senile dementia [1,2]. Additionally, the chronic consumption of statins for the control of hypercholesterolemia and cardiovascular risk results in secondary dyslipidemia myocytes inflammation [1,2].The common element that might explain the previously described complications and side effects in T2D diabetic patients is an axis of genes that encode for the system of transcytosis in the cellular membranes from small intestine, kidney, liver, striated muscle, and other tissues. The components of this transcytosis system are LRP2, AMN, CUBN, ARH, Dab2, GIPC, NHE3, ClC5, FcRn and NaPi-IIa, which mediate the reuptake of B complex vitamins, including folic acid among other molecules [3][4][5][6][7][8][9][10].The clinical effect of these genes might be seen in the development of different diseases or clinical conditions (Table 1). Mutations in LRP2 have been associated with diabetes, aminoglucosides response, DonnaiBarrow syndrome (DBS), Facio-oculo-acoustic-renal syndrome (FOAR) and Alzheimer's disease. While mutations in AMN and CUB occur with megaloblastic anemia plus albuminuria. CUBallelic variants are related to the progression of renal damage and ARH variations are associated with hypercholesterolemia [3][4][5][6][7][8][9][10]. NHE3 mutations show association with congenital sodium diarrhea, whereas ClC5 gene is related to renal failure or Dent disease. ClC5, FcRn, NaPi-IIa gene are related with metabolic renal disease. DAB2, GIPC has an uncertain meaning in human pathology, but their pathogenic effect must be explored [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].Considering the interaction between these genes...

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LRP2 mediates folate uptake in the developing neural tube

Cited by 45 publications

References 44 publications

Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes

Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes

Novel functions of folate receptor alpha in CNS development and diseases

Exploration of gene variations in the transcytosis system as a policy proposal for the personalized therapy in type 2 diabetes mellitus

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