BNIP‐2 binds phosphatidylserine, localizes to vesicles, and is transported by kinesin‐1

Akamatsu, Rie; Ishida-Kitagawa, Norihiro; Aoyama, Takane; Oka, Chio; Kawaichi, Masashi

doi:10.1111/gtc.12209

Cited by 5 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we show that KLC1 interacts with WAVE1, (BNIP-2), and protein interacting with APP tail 1 (PAT1) [1,8,10,14,21,22]. In this study, we have identified that WAVE1 interacted with the TPR domain of KLC1.…”

Section: Discussionmentioning

confidence: 70%

The Scaffolding Protein WAVE1 Associates with Kinesin 1 through the Tetratricopeptide Repeat (TPR) Domain of the Kinesin Light Chain (KLC)

Jang¹,

Jeong²,

Urm³

et al. 2016

Journal of Life Science

View full text Add to dashboard Cite

Kinesin superfamily proteins (KIFs) are microtubule-dependent molecular motor proteins essential for the intracellular transport of organelles and protein complexes in cells. Kinesin 1 is a member of those KIFs that transport various cargoes, including organelles, synaptic vesicles, neurotransmitter receptors, cell signaling molecules, and mRNAs through interaction between its light chain subunit and the cargoes. Kinesin light chains (KLCs) are non-motor subunits that associate with the kinesin heavy chain (KHC) dimer. KLCs interact with many different binding proteins, but their particular binding proteins have not yet been fully identified. We used the yeast two-hybrid assay to identify proteins that interact with the tetratricopeptide repeat (TPR) domain of KLC1. We found an interaction between the TPR domain of KLC1 and Wiskott-Aldrich syndrome protein family member 1 (WAVE1), a member of the WASP/WAVE family involved in regulation of actin cytoskeleton. WAVE1 bound to the six TPR domain-containing regions of KLC1 and did not interact with KHCs (KIF5A, KIF5B, and KIF5C) in the yeast two-hybrid assay. The carboxyl (C)-terminal verprolin-cofilin-acidic (VCA) domain of WAVE1 is essential for interaction with KLC1. Also, other WAVE isoforms (WAVE2 and WAVE3) interacted with KLC1 in the yeast two-hybrid assay. When co-expressed in HEK-293T cells, WAVE1 co-localized with KLC1 and co-immunoprecipitated with KLC1 and KIF5B. These results suggest that kinesin 1 motor protein may transport WAVE complexes or WAVE-coated cargoes in cells.

show abstract

Section: Discussionmentioning

confidence: 70%

The Scaffolding Protein WAVE1 Associates with Kinesin 1 through the Tetratricopeptide Repeat (TPR) Domain of the Kinesin Light Chain (KLC)

Jang¹,

Jeong²,

Urm³

et al. 2016

Journal of Life Science

View full text Add to dashboard Cite

show abstract

“…Potential Lipid-Binding Region in Y BCH. Previously it was shown that BNIP-2 binds to phosphatidylserine (a phospholipid) via its BCH domain, which implies that the BCH domain has lipid-binding properties (33). Moreover, the Sec14 domain of neurofibromin was highlighted in our N-terminal domain structural search as being homologous with the BCH domain.…”

Section: Resultsmentioning

confidence: 79%

Structural basis for p50RhoGAP BCH domain–mediated regulation of Rho inactivation

Chichili

Chew

Shankar

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Spatiotemporal regulation of signaling cascades is crucial for various biological pathways, under the control of a range of scaffolding proteins. The BNIP-2 and Cdc42GAP Homology (BCH) domain is a highly conserved module that targets small GTPases and their regulators. Proteins bearing BCH domains are key for driving cell elongation, retraction, membrane protrusion, and other aspects of active morphogenesis during cell migration, myoblast differentiation, and neuritogenesis. We previously showed that the BCH domain of p50RhoGAP (ARHGAP1) sequesters RhoA from inactivation by its adjacent GAP domain; however, the underlying molecular mechanism for RhoA inactivation by p50RhoGAP remains unknown. Here, we report the crystal structure of the BCH domain of p50RhoGAP Schizosaccharomyces pombe and model the human p50RhoGAP BCH domain to understand its regulatory function using in vitro and cell line studies. We show that the BCH domain adopts an intertwined dimeric structure with asymmetric monomers and harbors a unique RhoA-binding loop and a lipid-binding pocket that anchors prenylated RhoA. Interestingly, the β5-strand of the BCH domain is involved in an intermolecular β-sheet, which is crucial for inhibition of the adjacent GAP domain. A destabilizing mutation in the β5-strand triggers the release of the GAP domain from autoinhibition. This renders p50RhoGAP active, thereby leading to RhoA inactivation and increased self-association of p50RhoGAP molecules via their BCH domains. Our results offer key insight into the concerted spatiotemporal regulation of Rho activity by BCH domain–containing proteins.

show abstract

“…In addition, caytaxin is abundantly expressed in neurons of the cortex, cerebellum, hippocampus, olfactory bulb, and basal ganglia. 33 Akamatsu and colleagues used full-length caytaxin as a bait to perform yeast two-hybridization with mouse adult brain cDNA, 40 and found that caytaxin can drive the protein light chain of kinesin-1 through its N-terminal ELEWED sequence (amino acids 115-120) and participate in axonal transportation. Kinesin, a key molecule for axonal transportation, can be combined with a variety of linker molecules, such as TRAK1/2 and JIP1, to regulate mitochondrial axonal transportation of amyloid precursor protein.…”

Section: Ischemic Stroke Activates the Death-associated Protein Kinasmentioning

confidence: 99%

Death-associated Protein Kinase 1 Impairs the Hippocampo-prefrontal Cortical Circuit and Mediates Post-stroke Depression

Ke¹,

Ma²,

Zhang³

et al. 2018

Exploratory Research and Hypothesis in Medicine

View full text Add to dashboard Cite

Post-stroke depression (PSD) is a common and complex post-stroke neuropsychiatric disorder, which not only delays functional recovery but also increases mortality, and which currently lacks effective drug therapy. The pathogenesis of PSD is associated with impairment of the subcortical neural circuits and alterations of synaptic plasticity and neurotransmitters, but the exact mechanisms of PSD remain unknown. Our previous work indicates that the death-associated protein kinase 1 (DAPK1) mediates neuronal death after stroke. Genetic deletion of DAPK1 gene or blocking DAPK1 signal in the PSD mouse model can not only alleviate cerebral ischemic injury but also relieve PSD-like behaviors. Our previous work has also demonstrated the following results. First, the neural circuit of dorsal CA1 (dCA1) to medial prefrontal cortex (mPFC) (dCA1-mPFC) is selectively impaired after stroke. Second, the DAPK1 signal is involved in the impairment of dCA1-mPFC neural circuit after stroke. Third, genetic deletion of the DAPK1 gene or blocking of the DAPK1 signal alleviates the injury of dCA1-mPFC neural circuit after stroke and improves PSD-like behaviors. In conclusion, we hypothesize that activated DAPK1 signal after stroke induces apoptosis in the hippocampal dCA1 neurons, leading to loss of the dCA1-mPFC glutamatergic projections, synaptic injury, decrease of glutamate release, inhibition of mPFC neurons, and finally onset of PSD. We hope to further replenish the mechanisms of PSD and provide new insights for PSD treatment.

show abstract

BNIP‐2 binds phosphatidylserine, localizes to vesicles, and is transported by kinesin‐1

Cited by 5 publications

References 44 publications

The Scaffolding Protein WAVE1 Associates with Kinesin 1 through the Tetratricopeptide Repeat (TPR) Domain of the Kinesin Light Chain (KLC)

The Scaffolding Protein WAVE1 Associates with Kinesin 1 through the Tetratricopeptide Repeat (TPR) Domain of the Kinesin Light Chain (KLC)

Structural basis for p50RhoGAP BCH domain–mediated regulation of Rho inactivation

Death-associated Protein Kinase 1 Impairs the Hippocampo-prefrontal Cortical Circuit and Mediates Post-stroke Depression

Contact Info

Product

Resources

About