Browsing by Author "Kaplan, Oktay İsmail"

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ConVarT: A search engine for matching human genetic variants with variants from non-human species
(Oxford University Press, 2022) Pir, Mustafa; Bilgin, Halil I.; Sayıcı, Ahmet; Coşkun, Fatih; Torun, Furkan M; Zhao, Pei; Kang, Yahong; Çevik, Sebiha; Kaplan, Oktay İsmail; 0000-0002-8733-0920; 0000-0002-0935-1929; AGÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümü; Pİr, Mustafa; Bilgin, Halil İbrahim; Sayıcı, Ahmet; Coşkun, Fatih; Torun, Furkan M.; Çevik, Sebiha; Kaplan, Oktay İsmail
The availability of genetic variants, together with phenotypic annotations from model organisms, facilitates comparing these variants with equivalent variants in humans. However, existing databases and search tools do not make it easy to scan for equivalent variants, namely 'matching variants' (MatchVars) between humans and other organisms. Therefore, we developed an integrated search engine called ConVarT (http://www.convart.org/) for matching variants between humans, mice, and Caenorhabditis elegans. ConVarT incorporates annotations (including phenotypic and pathogenic) into variants, and these previously unexploited phenotypic MatchVars from mice and C. elegans can give clues about the functional consequence of human genetic variants. Our analysis shows that many phenotypic variants in different genes from mice and C. elegans, so far, have no counterparts in humans, and thus, can be useful resources when evaluating a relationship between a new human mutation and a disease.
Investigating the Impact of Birt–Hogg–Dubé Syndrome Associated Folliculin (FLCN) and Retinitis Pigmentosa 2 (RP2) Loss on Cilia Function and Morphology
(Cumhuriyet Üniversitesi, 2024) Kaplan, Oktay İsmail; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Kaplan, Oktay İsmail
Folliculin (FLCN), a GTPase-activating protein (GAP), has been linked to Birt–Hogg–Dubé syndrome, the mTORC1 signaling pathway and cilia. Disruptions in cilia structure and function lead to a group of diseases known as ciliopathies. Birt-Hogg-Dubé syndrome is one of 35 different ciliopathy diseases and there are more than 250 genes that cause ciliopathy diseases. FLCN interacts with kinesin-2 along cilia. The specific role of FLCN in regulating Kinesin-IFT trafficking has, however, remained unclear. In the current study, we investigated the effects of flcn-1 loss (the human ortholog of FLCN) on kinesin and IFT trafficking in C. elegans. The loss of flcn-1 alone did not result in any apparent alterations to kinesin or IFT trafficking within the cilia. However, when we combined the deletion of flcn-1 with the deletion of Retinitis Pigmentosa 2 (RP2), another GAP protein, the ciliary entry of a non-ciliary membrane protein TRAM-1 (Translocation Associated Membrane Protein 1) occured. Additionally, although cilia length was unaltered, our analysis of double mutants revealed the extra branch in wing AWB cilia morphology but not the single rod-like PHA/PHB cilia. In summary, our study reveals the previously unknown functions of FLCN in ciliary gating and cilia morphology in C. elegans
RPI-1 (human DCDC2) displays functional redundancy with Nephronophthisis 4 in regulating cilia biogenesis in C. elegans
(TUBİTAK, 2023) Kaplan, Oktay İsmail; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Kaplan, Oktay İsmail
Projecting from most cell surfaces, cilia serve as important hubs for sensory and signaling processes and have been linked to a variety of human disorders, including Bardet-Biedl Syndrome (BBS), Meckel-Gruber Syndrome (MKS), Nephronophthisis (NPHP), and Joubert Syndrome, and these diseases are collectively known as a ciliopathy. DCDC2 is a ciliopathy protein that localizes to cilia; nevertheless, our understanding of the role of DCDC2 in cilia is still limited. We employed C. elegans to investigate the function of C. elegans RPI-1, a Caenorhabditis elegans ortholog of human DCDC2, in cilia and found that C. elegans RPI-1 localizes to the entire ciliary axoneme, but is not present in the transition zone and basal body. We generated a null mutant of C. elegans rpi-1, and our analysis with a range of fluorescence-based ciliary markers revealed that DCDC2 and nephronophthisis 4 (NPHP-4/NPHP4) display functional redundant roles in regulating cilia length and cilia positions. Taken together, our analysis discovered a novel genetic interaction between two ciliopathy disease genes (RPI-1/DCDC2 and NPHP-4/NPHP4) in C. elegans.
WDR31 displays functional redundancy with GTPase-activating proteins (GAPs) ELMOD and RP2 in regulating IFT complex and recruiting the BBSome to cilium
(LIFE SCIENCE ALLIANCE LLC, 2023) Cevik, Sebiha; Peng, Xiaoyu; Beyer, Tina; Pir, Mustafa Samet; Yenisert, Ferhan; Woerz, Franziska; Hoffmann, Felix; Altunkaynak, Betul; Pir, Betul; Boldt, Karsten; Karaman, Asli; Cakiroglu, Miray; Oner, S. Sadik; Cao, Ying; Ueffing, Marius; Kaplan, Oktay İsmail; 0000-0002-0935-1929; 0000-0002-6302-8997; 0000-0002-4645-7626; 0000-0002-1028-8197; 0000-0002-2693-689X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Cevik, Sebiha; Pir, Mustafa Samet; Yenisert, Ferhan; Altunkaynak, Betul; Pir, Betul; Kaplan, Oktay İsmail
The correct intraflagellar transport (IFT) assembly at the ciliary base and the IFT turnaround at the ciliary tip are key for the IFT to perform its function, but we still have poor understanding about how these processes are regulated. Here, we identify WDR31 as a new ciliary protein, and analysis from zebrafish and Caeno-rhabditis elegans reveals the role of WDR31 in regulating the cilia morphology. We find that loss of WDR-31 together with RP-2 and ELMD-1 (the sole ortholog ELMOD1-3) results in ciliary accumu-lations of IFT Complex B components and KIF17 kinesin, with fewer IFT/BBSome particles traveling along cilia in both anterograde and retrograde directions, suggesting that the IFT/BBSome entry into the cilia and exit from the cilia are impacted. Furthermore, anterograde IFT in the middle segment travels at increased speed in wdr-31;rpi-2;elmd-1. Remarkably, a non-ciliary protein leaks into the cilia of wdr-31;rpi-2;elmd-1, possibly because of IFT de-fects. This work reveals WDR31-RP-2-ELMD-1 as IFT and BBSome trafficking regulators.