IndraLab

Statements

VAPA binds KCNB1. 21 / 21
| 21
sparser
"In contrast, TAT-DP-2 exposure induced a significant reduction in PLA reactions ( xref ), demonstrating that this peptide alone could effectively disrupt Kv2.1-VAPA association, seemingly without directly binding to VAPA."
| PMC
sparser
"The association of VAPA with Kv2.1 relies on a "two phenylalanines in an Acidic Tract" (FFAT) binding domain on VAPA, and a non-canonical phosphorylation-dependent FFAT motif comprising the Kv2-specific clustering or PRC motif."
30012696
sparser
"S5, B and C) suggests that DP-2’s declustering-inducing disruption of Kv2.1-VAPA association might occur via a unique mechanism and thus could lack significant off-target actions on the broad array of VAP-binding proteins."
| PMC
sparser
"In this work, we similarly identified the critical sequence within the Kv2.2 C-terminus that can disrupt Kv2.1-VAPA association, effectively removing the portal of entry for proapoptotic Kv2.1 channels reaching the membrane."
| PMC
sparser
"Despite the lack of demonstrable direct binding between TAT-DP-2 and VAPA, we evaluated whether TAT-DP-2 could still disrupt the Kv2.1-VAPA interaction in vitro, given its strong declustering effect."
| PMC
sparser
"TAT-DP-2, a membrane-permeable derivative, induces Kv2.1 surface cluster dispersal, prevents post-injurious pro-apoptotic potassium current enhancement, and is neuroprotective in vitro by disrupting the association of Kv2.1 with VAPA."
32937450
sparser
"We suggest that TAT-DP-2 induces Kv2.1 declustering by disrupting Kv2.1-VAPA association and scaffolding sites required for the membrane insertion of Kv2.1 channels following injury."
| PMC
sparser
"We suggest that TAT-DP-2 induces Kv2.1 declustering by disrupting Kv2.1-VAPA association and scaffolding sites required for the membrane insertion of Kv2.1 channels following injury."
32937450
sparser
"In a recent study, we exploited knowledge of this proapoptotic Kv2.1 surface insertion mechanism to validate the targeted-disruption of Kv2.1-VAPA association and cluster dispersal as a neuroprotective strategy [ xref ]."
| PMC
sparser
"Interestingly, disrupting the phosphorylation-dependent interaction between Kv2.1 and VAP-A ( xref ) is neuroprotective and prevents pro-apoptotic K + entry upon ischaemic injury ( xref )."
33681218
sparser
"We present the first evidence of targeted disruption of Kv2.1-VAPA association as a neuroprotective strategy following brain ischemia."
| PMC
sparser
"We present the first evidence of targeted disruption of Kv2.1-VAPA association as a neuroprotective strategy following brain ischemia."
32937450
sparser
"DP-2 alone does not bind to VAPA but effectively disrupts Kv2.1-VAPA association."
| PMC
sparser
"Following treatment, we used a PLA staining protocol that allowed for fluorescent labeling of Kv2.1-VAPA association based on published methods ( xref )."
| PMC
sparser
"It is also plausible that the actions of TAT-DP-2 require Kv2.1-VAPA association in the cellular cluster microdomain, while acellular experiments such as the peptide spot array do not provide a sufficiently realistic spatial and electrostatic articulation between key proteins."
| PMC
sparser
"Our data also present strong mechanistic evidence that disruption of Kv2.1-VAPA interaction by our peptide can account for the neuroprotective blockade of proapoptotic Kv2.1 potassium currents following injury (fig."
| PMC
sparser
"Although the PLAs in our study clearly show that TAT-DP-2 treatment reduces the interaction between Kv2.1 and VAPA, a peptide spot array assay argues that the active peptide fragment from DP-2 (SIDSFTS) does not bind to VAPA proteins directly, even when mutated into its pseudo-phosphorylated form."
| PMC
sparser
"We observed robust fluorescent PLA puncta formation in both vehicle and TAT-Sc-2–treated neurons ( xref ), indicating a high level of Kv2.1-VAPA association."
| PMC
sparser
"Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels."
32937450
sparser
"TAT-DP-2, a membrane-permeable derivative, induces Kv2.1 surface cluster dispersal, prevents post-injurious pro-apoptotic potassium current enhancement, and is neuroprotective in vitro by disrupting the association of Kv2.1 with VAPA."
| PMC
sparser
"S5, B and C) when compared with a scrambled sequence peptide, our results suggest that a more complex interaction between VAPA and Kv2.1 may be at play."
| PMC