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HSPC300 and its role in neuronal connectivity.

ABSTRACT: BACKGROUND:The WAVE/SCAR complex, consisting of CYFIP (PIR121 or Sra1), Kette (Nap1), Abi, SCAR (WAVE) and HSPC300, is known to regulate the actin nucleating Arp2/3 complex in a Rac1-dependent manner. While in vitro and in vivo studies have demonstrated that CYFIP, Kette, Abi and SCAR work as subunits of the complex, the role of the small protein HSPC300 remains unclear. RESULTS:In the present study, we identify the HSPC300 gene and characterize its interaction with the WAVE/SCAR complex in the Drosophila animal model. On the basis of several lines of evidence, we demonstrate that HSPC300 is an indispensable component of the complex controlling axonal and neuromuscular junction (NMJ) growth. First, the Drosophila HSPC300 expression profile resembles that of other members of the WAVE/SCAR complex. Second, HSPC300 mutation, as well as mutations in the other complex subunits, results in identical axonal and NMJ growth defects. Third, like with other complex subunits, defects in NMJ architecture are rescued by presynaptic expression of the respective wild-type gene. Fourth, HSPC300 genetically interacts with another subunit of the WAVE/SCAR complex. Fifth, HSPC300 physically associates with CYFIP and SCAR. CONCLUSION:Present data provide the first evidence for HSPC300 playing a role in nervous system development and demonstrate in vivo that this small protein works in the context of the WAVE/SCAR complex.

SUBMITTER: Qurashi A

PROVIDER: S-EPMC2098765 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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HSPC300 and its role in neuronal connectivity.

Qurashi Abrar A Sahin H Bahar HB Carrera Pilar P Gautreau Alexis A Schenck Annette A Giangrande Angela A

Neural development 20070925

<h4>Background</h4>The WAVE/SCAR complex, consisting of CYFIP (PIR121 or Sra1), Kette (Nap1), Abi, SCAR (WAVE) and HSPC300, is known to regulate the actin nucleating Arp2/3 complex in a Rac1-dependent manner. While in vitro and in vivo studies have demonstrated that CYFIP, Kette, Abi and SCAR work as subunits of the complex, the role of the small protein HSPC300 remains unclear.<h4>Results</h4>In the present study, we identify the HSPC300 gene and characterize its interaction with the WAVE/SCAR ...[more]

PMID: 17894861

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Project description:BackgroundAlzheimer's disease (AD) encompasses a spectrum that may progress from mild cognitive impairment (MCI) to full dementia, characterized by amyloid-beta and tau accumulation. Transcranial direct current stimulation (tDCS) is being investigated as a therapeutic option, but its efficacy in relation to individual genetic and biological risk factors remains underexplored.ObjectiveTo evaluate the effects of a two-week anodal tDCS regimen on the left dorsolateral prefrontal cortex, focusing on functional connectivity changes in neural networks in MCI patients resulting from various possible underlying disorders, considering individual factors associated to AD such as amyloid-beta deposition, APOE ϵ4 allele, BDNF Val66Met polymorphism, and sex.MethodsIn a single-arm prospective study, 63 patients with MCI, including both amyloid-PET positive and negative cases, received 10 sessions of tDCS. We assessed intra- and inter-network functional connectivity (FC) using fMRI and analyzed interactions between tDCS effects and individual factors associated to AD.ResultstDCS significantly enhanced intra-network FC within the Salience Network (SN) and inter-network FC between the Central Executive Network and SN, predominantly in APOE ϵ4 carriers. We also observed significant sex*tDCS interactions that benefited inter-network FC among females. Furthermore, the effects of multiple modifiers, particularly the interaction of the BDNF Val66Met polymorphism and sex, were evident, as demonstrated by increased intra-network FC of the SN in female Met non-carriers. Lastly, the effects of tDCS on FC did not differ between the group of 26 MCI patients with cerebral amyloid-beta deposition detected by flutemetamol PET and the group of 37 MCI patients without cerebral amyloid-beta deposition.ConclusionsThe study highlights the importance of precision medicine in tDCS applications for MCI, suggesting that individual genetic and biological profiles significantly influence therapeutic outcomes. Tailoring interventions based on these profiles may optimize treatment efficacy in early stages of AD.

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HSPC300 and its role in neuronal connectivity.

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HSPC300 and its role in neuronal connectivity.

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