CELLULAR FUNCTION OF THE ADP-RIBOSYLATION FACTOR 6 GTP BINDING PROTEIN
CELLULAR FUNCTION OF THE ADP-RIBOSYLATION FACTOR 6 GTP BINDING PROTEIN
批准号:
6109173
负责人:
Julie G Donaldson
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
adp -核糖基化因子(arf)是一个家族
英文摘要
The ADP-ribosylation factors (ARFs) are a family of
GTP binding proteins that regulate membrane traffic and organelle
structure in the cell. We have been studying the cellular function of
ARF6, an ARF that affects plasma membrane (PM) traffic and the
actin cytoskeleton. ARF6 regulates the movement of PM into and
out of a novel, endosomal recycling pathway. The return of
membrane to the PM requires ARF6 activation, occurs at discrete
sites along the peripheral edges of cells and is associated with the
formation of actin containing protrusions and membrane ruffling.
Formation of protrusions is exaggerated in HeLa cells
overexpressing ARF6 upon the addition of aluminum fluoride
(AlF), an activator of heterotrimeric G proteins. The AlF treatment
results in an accumulation of ARF6 at the PM, formation of
protrusive structures, and a block in internalization of PM into the
endosomal compartment. These are also characteristics of the effect
of expressing the constitutively active mutant of ARF6 in cells. To
investigate whether a G protein was responsible for this effect of
AlF and thus a potential upstream regulator of ARF6, we
cotransfected HeLa cells with ARF6 and constitutively active,
candidate G alpha proteins. G alpha q, but not Gs, Gi2, or G12,
appears to specifically activate ARF6 and recreates effects observed
with AlF. We are currently investigating the mechanism whereby
Gq maintains ARF6 in the activated state. In order to identify
domains in ARF6 responsible for its cellular localization and
function, we have constructed chimeras between ARF6 and ARF1
and expressed them in HeLa cells. ARF1 associates with Golgi
membranes and regulates traffic through and maintenance of the
Golgi complex. We found that the carboxyl- terminal halves of
ARF6 and ARF1 contain information for targeting them to the
correct membrane compartment, whereas the amino-terminal halves
contain information for coupling to effector functions. Although the
1-6 chimera (amino-terminal half of ARF1, carboxyl-terminal half
of ARF6) resembles ARF6 in it localization, it does not induce
protrusions upon the addition of AlF. However, substitution of 2
amino acid residues (QS) in the amino-terminal half of this 1-6
chimera results in a gain-of- function, where protrusions now form.
Mapping this effector domain to these two amino acids in ARF6
will facilitate the identification of interacting effector molecules and
development of inhibitory peptides or antibodies that can be used to
block ARF6 function.
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Pathways and itinerary of clathrin-independent endocytosis
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批准号:8746636
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项目类别:
-
资助金额:$5.63万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Mechanisms of Clathrin-Independent Endocytosis
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批准号:8746686
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项目类别:
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资助金额:$59.26万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:7968968
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项目类别:
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资助金额:$117.67万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:8939753
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项目类别:
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资助金额:$17.13万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Pathways and mechanisms of clathrin-independent endocytosis
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批准号:8149571
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项目类别:
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资助金额:$91.99万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:8557897
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项目类别:
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资助金额:$25.19万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Light Microscopy Core
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批准号:8746877
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项目类别:
-
资助金额:$108.2万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Pathways and itinerary of clathrin-independent endocytosis
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批准号:8344861
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项目类别:
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资助金额:$64.23万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Light Microscopy Core
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批准号:8558138
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项目类别:
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资助金额:$100.33万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:9354305
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项目类别:
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资助金额:$18.39万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:8746542
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项目类别:
-
资助金额:$13.65万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Mechanisms of Clathrin-Independent Endocytosis
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批准号:8558067
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项目类别:
-
资助金额:$67.17万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Mechanisms of Clathrin-Independent Endocytosis
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批准号:8939887
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项目类别:
-
资助金额:$68.53万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Mechanisms of Clathrin-Independent Endocytosis
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批准号:9354312
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项目类别:
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资助金额:$91.94万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Cellular Function Of The ADP-ribosylation Factor 6
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批准号:6966863
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:7321526
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:7734942
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项目类别:
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资助金额:$126.35万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:7154199
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:7594364
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项目类别:
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资助金额:$193.42万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
Arf GTP-binding proteins and membrane traffic
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批准号:8149467
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项目类别:
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资助金额:$30.66万
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财政年份:--
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负责人:Julie G Donaldson
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依托单位:
海外基金