Abstract
Scaffold proteins play a pivotal role in making protein complexes, and organize binding partners into a functional unit to enhance specific signaling pathways. IQ motif-containing GTPase activating protein 1 (IQGAP1) is an essential protein for spine formation due to its role in scaffolding multiple signal complexes. However, it remains unclear how IQGAP1 interacts within the brain. In the present study, we screened novel IQGAP1-interacting proteins by a proteomic approach. As a novel IQGAP1-interacting protein, we identified valosin-containing protein (VCP) which is a causative gene in patients with inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). The physiological interaction of IQGAP1 with VCP was confirmed by an immunoprecipitation assay. Both the N-terminal (N-half) and C-terminal (C-half) fragments of IQGAP1 interacted with the N-terminal region of VCP. Co-localization of IQGAP1 and VCP was observed in the growth corn, axonal shaft, cell body, and dendrites in cultured hippocampal neurons at 4 days in vitro (DIV4). In cultured neurons at DIV14, IQGAP1 co-localized with VCP in dendrites. When HEK293T cells were co-transfected with IQGAP1 and VCP, an immunoprecipitation assay revealed that binding of IQGAP1 with disease-related mutant (R155H or A232E) VCP was markedly reduced compared to wild-type (WT) VCP. These results suggest that reduction of IQGAP1 and VCP interaction may be associated with the pathophysiology of IBMPFD.
| Original language | English |
|---|---|
| Pages (from-to) | 1384-1389 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 493 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 02-12-2017 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
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Valosin-containing protein (VCP) is a novel IQ motif-containing GTPase activating protein 1 (IQGAP1)-interacting protein. / Itoh, Norimichi; Nagai, Taku; Watanabe, Takashi; Taki, Kentaro; Nabeshima, Toshitaka; Kaibuchi, Kozo; Yamada, Kiyofumi.
In: Biochemical and Biophysical Research Communications, Vol. 493, No. 4, 02.12.2017, p. 1384-1389.Research output: Contribution to journal › Article
TY - JOUR
T1 - Valosin-containing protein (VCP) is a novel IQ motif-containing GTPase activating protein 1 (IQGAP1)-interacting protein
AU - Itoh, Norimichi
AU - Nagai, Taku
AU - Watanabe, Takashi
AU - Taki, Kentaro
AU - Nabeshima, Toshitaka
AU - Kaibuchi, Kozo
AU - Yamada, Kiyofumi
PY - 2017/12/2
Y1 - 2017/12/2
N2 - Scaffold proteins play a pivotal role in making protein complexes, and organize binding partners into a functional unit to enhance specific signaling pathways. IQ motif-containing GTPase activating protein 1 (IQGAP1) is an essential protein for spine formation due to its role in scaffolding multiple signal complexes. However, it remains unclear how IQGAP1 interacts within the brain. In the present study, we screened novel IQGAP1-interacting proteins by a proteomic approach. As a novel IQGAP1-interacting protein, we identified valosin-containing protein (VCP) which is a causative gene in patients with inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). The physiological interaction of IQGAP1 with VCP was confirmed by an immunoprecipitation assay. Both the N-terminal (N-half) and C-terminal (C-half) fragments of IQGAP1 interacted with the N-terminal region of VCP. Co-localization of IQGAP1 and VCP was observed in the growth corn, axonal shaft, cell body, and dendrites in cultured hippocampal neurons at 4 days in vitro (DIV4). In cultured neurons at DIV14, IQGAP1 co-localized with VCP in dendrites. When HEK293T cells were co-transfected with IQGAP1 and VCP, an immunoprecipitation assay revealed that binding of IQGAP1 with disease-related mutant (R155H or A232E) VCP was markedly reduced compared to wild-type (WT) VCP. These results suggest that reduction of IQGAP1 and VCP interaction may be associated with the pathophysiology of IBMPFD.
AB - Scaffold proteins play a pivotal role in making protein complexes, and organize binding partners into a functional unit to enhance specific signaling pathways. IQ motif-containing GTPase activating protein 1 (IQGAP1) is an essential protein for spine formation due to its role in scaffolding multiple signal complexes. However, it remains unclear how IQGAP1 interacts within the brain. In the present study, we screened novel IQGAP1-interacting proteins by a proteomic approach. As a novel IQGAP1-interacting protein, we identified valosin-containing protein (VCP) which is a causative gene in patients with inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). The physiological interaction of IQGAP1 with VCP was confirmed by an immunoprecipitation assay. Both the N-terminal (N-half) and C-terminal (C-half) fragments of IQGAP1 interacted with the N-terminal region of VCP. Co-localization of IQGAP1 and VCP was observed in the growth corn, axonal shaft, cell body, and dendrites in cultured hippocampal neurons at 4 days in vitro (DIV4). In cultured neurons at DIV14, IQGAP1 co-localized with VCP in dendrites. When HEK293T cells were co-transfected with IQGAP1 and VCP, an immunoprecipitation assay revealed that binding of IQGAP1 with disease-related mutant (R155H or A232E) VCP was markedly reduced compared to wild-type (WT) VCP. These results suggest that reduction of IQGAP1 and VCP interaction may be associated with the pathophysiology of IBMPFD.
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UR - http://www.scopus.com/inward/citedby.url?scp=85030634069&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2017.09.159
DO - 10.1016/j.bbrc.2017.09.159
M3 - Article
C2 - 28970065
AN - SCOPUS:85030634069
VL - 493
SP - 1384
EP - 1389
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -