12 research outputs found
Ubiquilin-2 associates with ubiquitinated AMPA receptors for proteasomal degradation
Ubiquilin (UBQL) is a member of type 2 ubiquitin-like (UBL) protein family. They structurally contain an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated (UBA) domain. Ubiquilin 2 (UBQL2) physically associates with poly ubiquitinated proteins and delivers them to the proteasome for degradation. This protein has been shown to play an important role in the regulation of aggregation and degradation of various neurodegenerative disease-associated proteins. In this study, we looked into the role of the ubiquilin-2 proteins in the AMPA receptor ubiquitination and proteasomal degradation pathway. Our results indicate that UBQL2 overexpression decreases AMPAR levels in neurons and also reduces GluA1 expression in HEK 293T cells. Moreover, by co-immunoprecipitation we found that UBQL2 interacts with ubiquitinated AMPARs. We, therefore propose that UBQL2 brings AMPARs to the proteasome for degradation. Consistent with this notion, expression of UBQL2 P497H, a mutant form incapable of interaction with proteasome, causes accumulation of AMPA receptors. These results indicate a role for UBQL2 in associating with and directing ubiquitinated AMPA receptors to the proteasome for degradation.2020-08-09T00:00:00
ALS-associated KIF5A mutations abolish autoinhibition resulting in a toxic gain of function
Understandingthepathogenicmechanismsof diseasemutations is critical toadvancingtreatments.ALS-associated mutations in the gene encoding the microtubulemotor KIF5A result in skipping of exon 27 (KIF5ADExon27) and the encoding of a protein with a novel 39 amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C terminus of mutant KIF5A results in a constitutively active state. Furthermore,mutant KIF5A possesses altered protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative ALS mutations result in a toxic gain of function in the intracellular motor KIF5A that disrupts intracellular trafficking and neuronal homeostasis
Motion-Based Immunological Detection of Zika Virus Using Pt-Nanomotors and a Cellphone
Zika virus (ZIKV) infection is an
emerging pandemic threat to humans
that can be fatal in newborns. Advances in digital health systems
and nanoparticles can facilitate the development of sensitive and
portable detection technologies for timely management of emerging
viral infections. Here we report a nanomotor-based bead-motion cellphone
(NBC) system for the immunological detection of ZIKV. The presence
of virus in a testing sample results in the accumulation of platinum
(Pt)-nanomotors on the surface of beads, causing their motion in H<sub>2</sub>O<sub>2</sub> solution. Then the virus concentration is detected
in correlation with the change in beads motion. The developed NBC
system was capable of detecting ZIKV in samples with virus concentrations
as low as 1 particle/μL. The NBC system allowed a highly specific
detection of ZIKV in the presence of the closely related dengue virus
and other neurotropic viruses, such as herpes simplex virus type 1
and human cytomegalovirus. The NBC platform technology has the potential
to be used in the development of point-of-care diagnostics for pathogen
detection and disease management in developed and developing countries
Motion-Based Immunological Detection of Zika Virus Using Pt-Nanomotors and a Cellphone
Zika virus (ZIKV) infection is an
emerging pandemic threat to humans
that can be fatal in newborns. Advances in digital health systems
and nanoparticles can facilitate the development of sensitive and
portable detection technologies for timely management of emerging
viral infections. Here we report a nanomotor-based bead-motion cellphone
(NBC) system for the immunological detection of ZIKV. The presence
of virus in a testing sample results in the accumulation of platinum
(Pt)-nanomotors on the surface of beads, causing their motion in H<sub>2</sub>O<sub>2</sub> solution. Then the virus concentration is detected
in correlation with the change in beads motion. The developed NBC
system was capable of detecting ZIKV in samples with virus concentrations
as low as 1 particle/μL. The NBC system allowed a highly specific
detection of ZIKV in the presence of the closely related dengue virus
and other neurotropic viruses, such as herpes simplex virus type 1
and human cytomegalovirus. The NBC platform technology has the potential
to be used in the development of point-of-care diagnostics for pathogen
detection and disease management in developed and developing countries
Motion-Based Immunological Detection of Zika Virus Using Pt-Nanomotors and a Cellphone
Zika virus (ZIKV) infection is an
emerging pandemic threat to humans
that can be fatal in newborns. Advances in digital health systems
and nanoparticles can facilitate the development of sensitive and
portable detection technologies for timely management of emerging
viral infections. Here we report a nanomotor-based bead-motion cellphone
(NBC) system for the immunological detection of ZIKV. The presence
of virus in a testing sample results in the accumulation of platinum
(Pt)-nanomotors on the surface of beads, causing their motion in H<sub>2</sub>O<sub>2</sub> solution. Then the virus concentration is detected
in correlation with the change in beads motion. The developed NBC
system was capable of detecting ZIKV in samples with virus concentrations
as low as 1 particle/μL. The NBC system allowed a highly specific
detection of ZIKV in the presence of the closely related dengue virus
and other neurotropic viruses, such as herpes simplex virus type 1
and human cytomegalovirus. The NBC platform technology has the potential
to be used in the development of point-of-care diagnostics for pathogen
detection and disease management in developed and developing countries
Motion-Based Immunological Detection of Zika Virus Using Pt-Nanomotors and a Cellphone
Zika virus (ZIKV) infection is an
emerging pandemic threat to humans
that can be fatal in newborns. Advances in digital health systems
and nanoparticles can facilitate the development of sensitive and
portable detection technologies for timely management of emerging
viral infections. Here we report a nanomotor-based bead-motion cellphone
(NBC) system for the immunological detection of ZIKV. The presence
of virus in a testing sample results in the accumulation of platinum
(Pt)-nanomotors on the surface of beads, causing their motion in H<sub>2</sub>O<sub>2</sub> solution. Then the virus concentration is detected
in correlation with the change in beads motion. The developed NBC
system was capable of detecting ZIKV in samples with virus concentrations
as low as 1 particle/μL. The NBC system allowed a highly specific
detection of ZIKV in the presence of the closely related dengue virus
and other neurotropic viruses, such as herpes simplex virus type 1
and human cytomegalovirus. The NBC platform technology has the potential
to be used in the development of point-of-care diagnostics for pathogen
detection and disease management in developed and developing countries
Motion-Based Immunological Detection of Zika Virus Using Pt-Nanomotors and a Cellphone
Zika virus (ZIKV) infection is an
emerging pandemic threat to humans
that can be fatal in newborns. Advances in digital health systems
and nanoparticles can facilitate the development of sensitive and
portable detection technologies for timely management of emerging
viral infections. Here we report a nanomotor-based bead-motion cellphone
(NBC) system for the immunological detection of ZIKV. The presence
of virus in a testing sample results in the accumulation of platinum
(Pt)-nanomotors on the surface of beads, causing their motion in H<sub>2</sub>O<sub>2</sub> solution. Then the virus concentration is detected
in correlation with the change in beads motion. The developed NBC
system was capable of detecting ZIKV in samples with virus concentrations
as low as 1 particle/μL. The NBC system allowed a highly specific
detection of ZIKV in the presence of the closely related dengue virus
and other neurotropic viruses, such as herpes simplex virus type 1
and human cytomegalovirus. The NBC platform technology has the potential
to be used in the development of point-of-care diagnostics for pathogen
detection and disease management in developed and developing countries
Motion-Based Immunological Detection of Zika Virus Using Pt-Nanomotors and a Cellphone
Zika virus (ZIKV) infection is an
emerging pandemic threat to humans
that can be fatal in newborns. Advances in digital health systems
and nanoparticles can facilitate the development of sensitive and
portable detection technologies for timely management of emerging
viral infections. Here we report a nanomotor-based bead-motion cellphone
(NBC) system for the immunological detection of ZIKV. The presence
of virus in a testing sample results in the accumulation of platinum
(Pt)-nanomotors on the surface of beads, causing their motion in H<sub>2</sub>O<sub>2</sub> solution. Then the virus concentration is detected
in correlation with the change in beads motion. The developed NBC
system was capable of detecting ZIKV in samples with virus concentrations
as low as 1 particle/μL. The NBC system allowed a highly specific
detection of ZIKV in the presence of the closely related dengue virus
and other neurotropic viruses, such as herpes simplex virus type 1
and human cytomegalovirus. The NBC platform technology has the potential
to be used in the development of point-of-care diagnostics for pathogen
detection and disease management in developed and developing countries