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Involvement of cortactin in regulati...

Karginov, Andrei Vladimirovich.

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Involvement of cortactin in regulation of the actin cytoskeleton and endocytosis.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Involvement of cortactin in regulation of the actin cytoskeleton and endocytosis./
作者:	Karginov, Andrei Vladimirovich.
面頁冊數:	190 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0088.
Contained By:	Dissertation Abstracts International66-01B.
標題:	Biology, Microbiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3161276
ISBN:	9780496950362

Involvement of cortactin in regulation of the actin cytoskeleton and endocytosis.
Karginov, Andrei Vladimirovich.

Involvement of cortactin in regulation of the actin cytoskeleton and endocytosis. - 190 p.

Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0088.

Thesis (Ph.D.)--University of Virginia, 2005.

Dynamic remodeling of the dendritic actin network is an important process in the regulation of membrane protrusion formation, cell motility, endocytosis and vesicle trafficking. Cortactin, a filamentous-actin binding protein, associates with dynamic actin structures at the cell periphery. Furthermore, cortactin interacts with the large GTPase dynamin, thus representing a candidate protein to link the actin cytoskeleton to the endocytic machinery.

ISBN: 9780496950362Subjects--Topical Terms:

1017734
Biology, Microbiology.

Involvement of cortactin in regulation of the actin cytoskeleton and endocytosis.
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245 1 0 $a Involvement of cortactin in regulation of the actin cytoskeleton and endocytosis.
300 $a 190 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0088.
500 $a Adviser: J. Thomas Parsons.
502 $a Thesis (Ph.D.)--University of Virginia, 2005.
520 $a Dynamic remodeling of the dendritic actin network is an important process in the regulation of membrane protrusion formation, cell motility, endocytosis and vesicle trafficking. Cortactin, a filamentous-actin binding protein, associates with dynamic actin structures at the cell periphery. Furthermore, cortactin interacts with the large GTPase dynamin, thus representing a candidate protein to link the actin cytoskeleton to the endocytic machinery.
520 $a The work presented in this dissertation demonstrates that cortactin modulates actin polymerization and influences the structure of the actin network via an interaction with the Arp2/3 complex. The cortactin N-terminal acidic (NTA) domain directly associates with the Arp2/3 complex and stimulates the ability to facilitate actin polymerization. A conserved DDW motif in the cortactin NTA domain is important for binding and activation of the Arp2/3 complex. Cortactin promotes Arp2/3-mediated branching of actin filaments and stabilizes the branched structures.
520 $a Additionally, we provide evidence that cortactin regulates transferrin endocytosis and recycling. The results suggest that this regulation depends upon interactions with the Arp2/3 complex and dynamin. Overexpression of wild-type cortactin inhibits transferrin endocytosis and recycling. Mutations that abolish the interactions of cortactin with the Arp2/3 complex (W22A) or its SH3 domain binding partners (W525K) dramatically diminish the inhibitory effect. Inhibition of transferrin uptake by overexpression of the cortactin SH3 domain is restored by introduction of a W525K mutation or by co-expression of dynamin. Downregulation of cortactin expression by RNA interference silencing results in an increased accumulation of transferrin at steady-state and the apparent inhibition of transferrin recycling. Acidification of cellular endosomes by treatment with acetate buffer (pH 5.0) partially reverses the inhibitory effect.
520 $a Based on the obtained data, we suggest that cortactin regulates the transport of endocytic vesicles to intracellular target compartments by modulating actin polymerization and the stability of the actin network.
590 $a School code: 0246.
650 4 $a Biology, Microbiology. $3 1017734
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791 $a Ph.D.
792 $a 2005
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