• Molecules and Cells
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• 제22권2호
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• pp.146-153
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• 2006

Cell polarity is critical for the division, differentiation, migration, and signaling of eukaryotic cells. RAX2 of budding yeast encodes a membrane protein localized at the cell cortex that helps maintain the polarity of the bipolar pattern. Here, we designate SPAC6f6.06c as $rax2^+$ of Schizosaccharomyces pombe, based on its sequence homology with RAX2, and examine its function in cell polarity. S. pombe $rax2^+$ is not essential, but ${\Delta}rax2$ cells are slightly smaller and grow slower than wild type cells. During vegetative growth or arrest at G1 by mutation of cdc10, deletion of $rax2^+$ increases the number of cells failing old end growth just after division. In addition, this failure of old end growth is dramatically increased in ${\Delta}tea1{\Delta}rax2$, pointing to genetic interaction of $rax2^+$ with $tea1^+$. ${\Delta}rax2$ cells contain normal actin and microtubule cytoskeletons, but lack actin cables, and the polarity factor for3p is not properly localized at the growing tip. In ${\Delta}rax2$ cells, and endogenous rax2p is localized at the cell cortex of growing cell tips in an actin- and microtubule-dependent manner. However, ${\Delta}rax2$ cells show no defects in cell polarity during shmoo formation and conjugation. Taken together, these observations suggest that rax2p controls the cell polarity of fission yeast during vegetative growth by regulating for3p localization.

• 생명과학회지
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• 제21권5호
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• pp.621-626
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• 2011

AMPK는 catalytic ${\alpha}$ subunit과 regulatory ${\beta}$ 및 ${\gamma}$ subunit으로 구성된 인산화 효소로, 그 동안 생체 내 중요 대사 조절자로써 연구되어 왔으나, 최근 유전학 연구를 통해 지금까지 밝혀지지 아니한 새로운 생체기능을 가짐이 밝혀졌다. 본 연구에서 초파리 유전학 기법을 활용하여 AMPK ${\gamma}$ subunit 유전자가 결손된 모델 초파리를 제작 하여 연구한 결과, AMPK ${\gamma}$ 유전자 결손 시 초파리 embryo의 표피형성이 심각하게 저해됨을 발견하였고, 조직학적 실험을 통해 표피세포의 극성이 AMPK ${\gamma}$ 유전자 결손 초파리에서 손상되어 있음을 확인하였다. 또한 세포극성을 조절하는 중요 분자인 MRLC의 인산화 또한 AMPK ${\gamma}$ 유전자 결손 시 저해되었으며, AMPK ${\gamma}$ 유전자 재도입 시 MRLC인산화와 표피세포의 극성이 모두 회복됨이 확인되어, 초파리 표피세포의 극성유지에 AMPK ${\gamma}$ 유전자가 필수적 임을 확인하였다.

• Journal of Microbiology
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• 제44권3호
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• pp.311-319
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• 2006

Bud6p is a component of a polarisome that controls cell polarity in Saccharomyces cerevisiae. In this study, we investigated the role of the Candide albicans Bud6 protein (CaBud6p) in cell polarity and hyphal development. CaBud6p, which consists of 703 amino acids, had 37% amino-acid sequence identity with the Bud6 protein of S. cerevisiae. The homozygous knock-out of CaBUD6 resulted in several abnormal phenotypes, such as a round and enlarged cells, widened bud necks, and a random budding pattern. In hypha-inducing media, the mutant cells had markedly swollen tips and a reduced ability to switch from yeast to hypha. In addition, a yeast two-Hybrid analysis showed a physical interaction between CaBud6p and CaAct1p, which suggests that CaBud6p may be involved in actin cable organization, like Bud6p in S. cerevisiae. Taken together, these results indicate that CaBud6 plays an important role in the polarized growth of C. albicans.

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.291-300
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• 2024

Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.

• Molecules and Cells
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• 제44권3호
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• pp.168-178
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• 2021

The retinal pigment epithelium (RPE) forms a monolayer sheet separating the retina and choroid in vertebrate eyes. The polarized nature of RPE is maintained by distributing membrane proteins differentially along apico-basal axis. We found the distributions of these proteins differ in embryonic, post-natal, and mature mouse RPE, suggesting developmental regulation of protein trafficking. Thus, we deleted tumor susceptibility gene 101 (Tsg101), a key component of endosomal sorting complexes required for transport (ESCRT), in embryonic and mature RPE to determine whether ESCRT-mediated endocytic protein trafficking correlated with the establishment and maintenance of RPE polarity. Loss of Tsg101 severely disturbed the polarity of RPE, which forms irregular aggregates exhibiting non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling. These findings suggest that ESCRT-mediated protein trafficking is essential for the development and maintenance of RPE cell polarity.

• Anatomy and Cell Biology
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• 제55권2호
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• pp.229-238
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• 2022

Cell migration is an essential process in embryonic development, wound healing, and pathological conditions. Our knowledge of cell migration is often based on the two dimentional evaluation of cell movement, which usually differs from what occurred in vivo. In this study, we investigated cellular migration from blastema tissue toward bovine decellularized mesentery tissue. In this regard, fibronectin (FN) was assessed to confirm cell migration. Therefore, we established a cell migration model using blastema cells migration toward the extracellular matrix derived from bovine mesenteric tissue. A physiochemical decellularization method was utilized based on freeze-thaw cycles and agitation in sodium dodecyl sulfate and Triton X-100 to remove cells from the extracellular matrix (ECM) of bovine mesenteric tissue. These types of matrices were assembled by the rings of blastema tissues originated from the of New Zealand rabbits pinna and cultured in a medium containing FN in different days in vitro, and then they are histologically evaluated, and the expression of the Tenascin C gene is analyzed. By means of tissue staining and after confirmation of the cell removal from mesenteric tissue, polarity, and migration of blastema cells was observed in the interaction site with this matrix. Also, the expression of the Tenascin C gene was assessed on days 15 and 21 following the cell culture process. The results showed that the three dimentional model of cellular migration of blastema cells along with the ECM could be a suitable model for investigating cell behaviors, such as polarity and cell migration in vitro.

• BMB Reports
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• 제43권2호
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• pp.69-78
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• 2010

Asymmetric cell division is a fundamental mechanism for the generation of body axes and cell diversity during early embryogenesis in many organisms. During intrinsically asymmetric divisions, an axis of polarity is established within the cell and the division plane is oriented to ensure the differential segregation of developmental determinants to the daughter cells. Studies in the nematode Caenorhabditis elegans have contributed greatly to our understanding of the regulatory mechanisms underlying cell polarity and asymmetric division. However, much remains to be elucidated about the molecular machinery controlling the spatiotemporal distribution of key components. In this review we discuss recent findings that reveal intricate interactions between translational control and targeted proteolysis. These two mechanisms of regulation serve to carefully modulate protein levels and reinforce asymmetries, or to eliminate proteins from certain cells.

• BMB Reports
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• 제51권9호
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• pp.425-426
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• 2018

As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to ${\beta}-catenin$ in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains unidentified. Recently, we reported that the Dishevelled (DVL), a key scaffolding protein between canonical and non-canonical Wnt pathway, is responsible for nuclear export of phosphorylated YAP. The DVL is also required for YAP intracellular trafficking induced by E-cadherin, ${\alpha}-catenin$, or metabolic stress. Note that the p53/LATS2 and LKB1/AMPK tumor suppressor axes, commonly inactivated in human cancer, govern the reciprocal inhibition between DVL and YAP. Conversely, loss of the tumor suppressor allows co-activation of YAP and Wnt independent of epithelial polarity or contact inhibition in human cancer. These observations provide novel mechanistic insight into (1) a tight molecular connection merging the Wnt and Hippo pathways, and (2) the importance of tumor suppressor contexts with respect to controlled proliferation and epithelial polarity regulated by cell adhesion.

• Korean Chemical Engineering Research
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• 제58권1호
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• pp.122-126
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• 2020

본 연구에서는 폴리디메틸실록산(PDMS)과 모세관-미세몰딩(MIMIC) 기술을 활용하여 마이크로패턴 채널 시스템을 제작하고, 단일 세포 수준에서 극성화 패턴으로 형성되는 분자 신호를 고해상도 세포 이미징을 통해 분석하였다. 이 과정에서 혈소판유래성장인자(PDGF)가 처리된 세포에서는 세포 이동에 중요한 세 종류의 신호인 포스포이노시티드 3-인산화효소(PI3K), Rac 및 액틴(Actin) 신호가 선두(front)영역에서 후미(rear)영역에 비해 강하게 활성화 하는 데 반해, 마이오신 경쇄(MLC) 신호는 비특이적 경향성을 보여주었다. 본 연구 결과는 향후 마이크로패턴의 미세환경에서 세포 극성화 신호와 세포 이동과의 상관 관계를 연구하는 데 중요한 도움이 될 것으로 사료된다.

• 생명과학회지
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• 제23권8호
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• pp.970-977
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• 2013

Epithelial-to-mesenchymal transition (EMT)는 embryogenesis에서 중요한 역할을 하며 tumor metastasis, invasion에도 관여함으로써 tumor progression 및 aggressiveness에 기여한다. EMT는 EMT hallmark인 epithelial E-cadherin의 발현 감소와 mesenchymal-like cell morphology를 획득함으로써 epithelial cell polarity를 잃어버리는 특징을 가지고 있다. $O_2{^-}$, $H_2O_2$, $OH^-$와 같은 활성산소가 EMT를 유도하는 것으로 알려져 있다. Snail이 E-cadherin의 발현을 억제함으로써 ROS에 의한 EMT에 관여하는 것으로 알려져 있으나, 그 기작은 완전히 밝혀져 있지 않다. 본 연구에서는, noninvasive breast tumor cell line인 MCF-7 세포에 Egr-1을 과발현시킨 후 그 영향을 조사하였다. Egr-1이 과발현되면, MCF-7 세포는 epithelial cell polarity를 잃고 spindle-shaped로 변화되므로, Egr-1이 EMT를 유도할 가능성이 대두되었다. 또한 Snail이 Egr-1에 의한 EMT에 관여함을 확인하였다. 나아가, 본 연구진은 Egr-1-Snail axis가 ROS에 의해 활성화 되고, ROS에 의한 EMT에서 중요한 역할을 함을 발견하였다.