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1

Subcellular localization of UDP-GlcNAc, UDP-Gal and SLC35B4 transporters

100%

Maszczak-Seneczko D., Olczak T., Olczak M.

Acta Biochimica Polonica

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2011

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vol. 58

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issue 3

413-419

EN

The mechanisms of transport and distribution of nucleotide sugars in the cell remain unclear. In an attempt to further characterize nucleotide sugar transporters (NSTs), we determined the subcellular localization of overexpressed epitope-tagged canine UDP-GlcNAc transporter, human UDP-Gal transporter splice variants (UGT1 and UGT2), and human SLC35B4 transporter splice variants (longer and shorter version) by indirect immunofluorescence using an experimental model of MDCK wild-type and MDCK-RCAr mutant cells. Our studies confirmed that the UDP-GlcNAc transporter was localized to the Golgi apparatus only and its localization was independent of the presence of endogenous UDP-Gal transporter. After overexpression of UGT1, the protein colocalized with the Golgi marker only. When UGT2 was overexpressed, the protein colocalized with the endoplasmic reticulum (ER) marker only. When UGT1 and UGT2 were overexpressed in parallel, UGT1 colocalized with the ER and Golgi markers and UGT2 with the ER marker only. This suggests that localization of the UDP-Gal transporter may depend on the presence of the partner splice variant. Our data suggest that proteins involved in nucleotide sugar transport may form heterodimeric complexes in the membrane, exhibiting different localization which depends on interacting protein partners. In contrast to previously published data, both splice variants of the SLC35B4 transporter were localized to the ER, independently of the presence of endogenous UDP-Gal transporter.

2

Endoplasmic reticulum quality control and apoptosis.

100%

Groenendyk J., Michalak M.

Acta Biochimica Polonica

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2005

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vol. 52

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issue 2

381-395

EN

The ER is one of the most important folding compartments within the cell, as well as an intracellular Ca^(2+) storage organelle and it contains a number of Ca^(2+) regulated molecular chaperones responsible for the proper folding of glycosylated as well as non-glycosylated proteins. The luminal environment of the ER contains Ca^(2+) which is involved in regulating chaperones such as calnexin and calreticulin, as well as apoptotic proteins caspase-12 and Bap31, which may play an important role in determining cellular sensitivity to ER stress and apoptosis. The ER quality control system consists of several molecular chaperones, including calnexin, that assist in properly folding proteins and transporting them through the ER as well as sensing misfolded proteins, attempting to refold them and if this is not possible, targeting them for degradation. Accumulation of misfolded protein in the ER leads to activation of genes responsible for the expression of ER chaperones. The UPR mechanism involves transcriptional activation of chaperones by the membrane-localized transcription factor ATF6, in conjunction with the ER membrane kinase IRE1, as well as translational repression of protein synthesis by another ER membrane kinase PERK. When accumulation of misfolded protein becomes toxic, apoptosis is triggered, potentially with IRE1 involved in signaling via caspase-12. Both the extrinsic and intrinsic apoptotic pathways appear to culminate in the activation of caspases and this results in the recruitment of mitochondria in an essential amplifying manner. Bap31 may direct pro-apoptotic crosstalk between the ER and the mitochondria via Ca^(2+) in conjunction with caspase-12 and calnexin. Accordingly, ER stress and the resultant Ca^(2+) release must be very carefully regulated because of their effects in virtually all areas of cell function.

3

The role of proteotoxic stress in vascular dysfunction in the pathogenesis of Alzheimer’s disease

63%

Fonseca A. C. R. G., Resende R., Cardoso S. M., Pereira C. F.

Endoplasmic Reticulum Stress in Diseases

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2015

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vol. 2

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issue 1

EN

Alzheimer’s disease (AD) is the principal cause of dementia in the elderly; however, its prevalence is increasing due to the fact that current pharmaceuticals used to manage the symptoms are not capable of preventing, halting, or reversing disease progression. In the last decade, evidence has accumulated to support the hypothesis that a primary cerebral vascular dysfunction initiates the cascade of events that leads to neuronal injury and the subsequent cognitive decline observed in AD. The mechanisms underlying these vascular defects and their relationship with neurodegeneration are still poorly understood however. It is pathologically known that cerebrovascular dysfunctions can induce the deposition of amyloid-β (Aβ), an amyloidogenic and toxic peptide that in turn causes cerebrovascular degeneration. Mammalian cells regulate proteostasis and the functioning of intracellular organelles through diverse mechanisms such as the Unfolded Protein Response, the Ubiquitin-Proteasome System and autophagy; however, when these mechanisms cannot compensate for perturbations in homeostasis, the cell undergoes programmed death via apoptosis. This review summarizes recent studies that together correlate the deregulation of protein quality control pathways with dysfunction of vascular endothelial cells of the brain in AD, thus supporting the hypothesis that it is the vicious, progressive failure of the proteostatic network and endothelial activation that underlies the cerebrovascular changes that symptomize AD.

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2 Acta Biochimica Polonica

1 Endoplasmic Reticulum Stress in Diseases

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1 Fonseca A. C. R. G.

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1 Maszczak-Seneczko D.

1 Michalak M.

1 Olczak M.

1 Olczak T.

1 Pereira C. F.

1 Resende R.

Subcellular localization of UDP-GlcNAc, UDP-Gal and SLC35B4 transporters

Endoplasmic reticulum quality control and apoptosis.

The role of proteotoxic stress in vascular dysfunction in the pathogenesis of Alzheimer’s disease