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A genetic dissection of Aip1p's interactions leads to a model for Aip1p-cofilin cooperative activities.

ABSTRACT: Actin interacting protein 1 (Aip1p) and cofilin cooperate to disassemble actin filaments in vitro and are thought to promote rapid turnover of actin networks in vivo. The precise method by which Aip1p participates in these activities has not been defined, although severing and barbed-end capping of actin filaments have been proposed. To better describe the mechanisms and biological consequences of Aip1p activities, we undertook an extensive mutagenesis of AIP1 aimed at disrupting and mapping Aip1p interactions. Site-directed mutagenesis suggested that Aip1p has two actin binding sites, the primary actin binding site lies on the edge of its N-terminal beta-propeller and a secondary actin binding site lies in a comparable location on its C-terminal beta-propeller. Random mutagenesis followed by screening for separation of function mutants led to the identification of several mutants specifically defective for interacting with cofilin but still able to interact with actin. These mutants suggested that cofilin binds across the cleft between the two propeller domains, leaving the actin binding sites exposed and flanking the cofilin binding site. Biochemical, genetic, and cell biological analyses confirmed that the actin binding- and cofilin binding-specific mutants are functionally defective, whereas the genetic analyses further suggested a role for Aip1p in an early, internalization step of endocytosis. A complementary, unbiased molecular modeling approach was used to derive putative structures for the Aip1p-cofilin complex, the most stable of which is completely consistent with the mutagenesis data. We theorize that Aip1p-severing activity may involve simultaneous binding to two actin subunits with cofilin wedged between the two actin binding sites of the N- and C-terminal propeller domains.

SUBMITTER: Clark MG

PROVIDER: S-EPMC1415301 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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A genetic dissection of Aip1p's interactions leads to a model for Aip1p-cofilin cooperative activities.

Clark Michael G MG Teply Joseph J Haarer Brian K BK Viggiano Susan C SC Sept David D Amberg David C DC

Molecular biology of the cell 20060118 4

Actin interacting protein 1 (Aip1p) and cofilin cooperate to disassemble actin filaments in vitro and are thought to promote rapid turnover of actin networks in vivo. The precise method by which Aip1p participates in these activities has not been defined, although severing and barbed-end capping of actin filaments have been proposed. To better describe the mechanisms and biological consequences of Aip1p activities, we undertook an extensive mutagenesis of AIP1 aimed at disrupting and mapping Aip ...[more]

PMID: 16421248

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Project description:AimsThe aim of the present study was to evaluate the performance of 'high'-'low' yielding pyramided lines (PLs), having the same combinations of qDTYs in Samba Mahsuri, MR219 and IR64-Sub1 genetic backgrounds, and to understand the genetic interactions among QTL and/with genetic background affecting grain yield.BackgroundEpistasis regulates the expression of traits governed by several major/minor genes/QTL. Multiple pyramided lines (PLs) with the same grain yield QTL (qDTYs) combinations but possessing grain yield variability under different levels of reproductive stage drought stress were identified in different rice genetic backgrounds at International Rice Research Institute (IRRI).ObjectivesThe objectives of the present study were to evaluate the performance pyramided lines (PLs) with drought QTL in the backgrounds of Samba Mahsuri, MR219 and IR64-Sub1 under reproductive stage drought stress (RS) and NS (non-stress) conditions, to understand the effect of epistatic interactions among qDTYs and with genetic background on GY under the differential level of stress and to identify the promising drought-tolerant lines with high yield under drought and higher background recovery in different genetic backgrounds.MethodsThe experiments were conducted in 2015 DS (dry season), 2015 WS (wet season) and 2017 DS at IRRI, Los Baños, Philippines, in a transplanted lowland ecosystem under lowland severe stress (LSS), lowland moderate stress (LMS) and lowland non-stress (LNS). The experiments were laid out in alpha lattice design with two replications.ResultsSeveral digenic interactions were found in different genetic backgrounds, 13 interactions in Samba Mahsuri, 11 in MR219 and 20 in IR64-Sub1 backgrounds. Among all digenic interactions, one QTL × QTL interaction, 17 QTL × background and 26 background × background interactions resulted in GY reduction in low yielding PLs in different genetic backgrounds under LSS or LMS. Negative interaction of qDTY3.1 , qDTY4.1 and qDTY9.1 with background markers and background × background interactions caused up to 15% GY reduction compared to the high yielding PLs under LMS in the Samba Mahsuri PLs. In MR219 PLs, the negative interaction of qDTY2.2 , qDTY3.2 , qDTY4.1 and qDTY12.1 with the background marker interval RM314-RM539, RM273-RM349 and RM445-RM346, RM473D-RM16, respectively resulted 52% GY reduction compared to the high yielding PLs under LSS. In IR64-Sub1 PLs, qDTY6.1 interacted with background loci at RM16-RM135, RM228-RM333, RM202-RM287 and RM415-RM558A marker interval under LSS and at RM475-RM525 marker interval under LMS, causing GY reduction to 58% compared to the high yielding PLs.ConclusionHigh yielding PLs in Samba Mahsuri (IR 99734:1-33-69-1-22-6), MR219 (IR 99784-156-87-2-4-1) and IR64-Sub1 (IR 102784:2-89-632-2-1-2) backgrounds without any negative interactions were identified. The identified selected promising PLs may be used as potential drought-tolerant donors or may be released as varieties for drought-prone ecosystems in different countries.

Dataset Information

A genetic dissection of Aip1p's interactions leads to a model for Aip1p-cofilin cooperative activities.

Publications

A genetic dissection of Aip1p's interactions leads to a model for Aip1p-cofilin cooperative activities.

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