Regulation of dynamin family proteins by post-translational modifications

Kar, Usha Pallabi; Dey, Himani; Rahaman, Abdur

doi:10.1007/s12038-017-9680-y

Cited by 17 publications

(17 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The large scale phosphoproteomic screens have identified multiple tyrosine phosphorylation sites of DYNAMIN, such as that occurring at pY 80 , pY 125 , pY 354 and pY 597 (Ballif et al, 2008) (Mallozzi et al, 2013). Among them, the Y 597 was a wellstudied phosphorylation site of DYNAMIN, which was previously reported to increase selfassembly and GTP hydrolysis in both DYNAMIN1 and 2 (Kar et al, 2017). However, the Y 597 of DYNAMIN was probably not the target of PTP-MEG2 because the interaction of Y 597 or A 597 with PTP-MEG2 exhibited no significant differences.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have identified that phosphorylation of DYNAMIN close to the G domain significantly increased its GTPase activity, thus promoting endocytosis (Kar et al, 2017). We therefore hypothesized that the phosphorylation of the DYNAMIN2 pY 125 site increased pore fission by up-regulating its GTPase activity, whereas dephosphorylation of DYNAMIN2 pY 125 site by PTP-MEG2 reversed it.…”

Section: Dynamin2-py 125mentioning

confidence: 91%

See 1 more Smart Citation

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates

Chen

Yang

et al. 2019

Preprint

View full text Add to dashboard Cite

41The tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory 42 mechanism for exocytosis. However, the participation of tyrosine phosphatases in 43 different exocytosis stages has not been defined. Here, we demonstrated that PTP-MEG2 44 controls multiple steps of catecholamine secretion. Biochemical and crystallographic 45 analysis revealed key residues that govern the PTP-MEG2 and NSF-pY 83 site interactions, 46 specify PTP-MEG2 substrate selectivity and modulate the fusion of catecholamine-47 containing vesicles. Unexpectedly, delineation of the PTP-MEG2 mutants along with the 48 NSF interface revealed that PTP-MEG2 controls the fusion pore opening through another 49 unknown substrate. Utilizing a bioinformatics search and biochemical and 50 electrochemical screening, we uncovered that PTP-MEG2 regulates the opening and 51 extension of the fusion pore by dephosphorylating the MUNC18-1 Y 145 site, which is 52 associated with epileptic encephalopathy. The crystal structure of the PTP-53 MEG2/phospho-MUNC18-1-pY 145 segment confirmed the interaction of PTP-MEG2 with 54MUNC18-1 through a distinct structural basis. Our studies extended mechanism insights 55 in complex exocytosis processes. 56 57 KEY WORDS: 58 59 exocytosis, tyrosine phosphorylation, structure, catecholamine, PTP-MEG2 60 61 HIGHLIGHTS: 62 63 PTP-MEG2 regulates multiple steps of exocytosis. 64 A crystal structure of the PTP-MEG2/phosphor-NSF-pY 83 segment was obtained. 65 Functional delineation of the PTP-MEG2/NSF interface resulted in uncovering unknown 66 PTP-MEG2 substrates. 67 PTP-MEG2 regulates fusion pore opening and extension through the MUNC18-1 pY 145 68 site. 69 The distinct structural bases of the recognition of substrates by PTP-MEG2 allows 70 selective inhibitor design. 71 72 73 74 75physiological processes (Wu et al., 2014, Dittman and Ryan, 2019, Neher and Brose, 2018. 79The contents of secreted vesicles include neuronal transmitters, immune factors and other 80 hormones (Alvarez de Toledo et al., 1993, Sudhof, 2013, Magadmi et al., 2019. There are three 81 main exocytosis pathways in secretory cells, namely, full-collapse fusion, kiss-and-run, and 82 compound exocytosis, which possess different secretion rates and lease amount (Sudhof, 2004). 83It was previously reported that the phosphorylation of critical proteins at serine/threonine or 84 tyrosine residues participated in stimulus-secretion coupling in certain important exocytosis 85 processes, for example, the secretion of insulin from pancreatic β cells and of catecholamine 86 from the adrenal medulla (Ortsater et al., 2014, Seino et al., 2009, Laidlaw et al., 2017. 87However, the exact roles of protein tyrosine phosphatases (PTPs) in the regulation of key 88 hormone secretion procedures are not fully understood. 89The 68-kDa PTP-MEG2, encoded by ptpn9, is a non-receptor classical PTP encompassing a 90 unique N-terminal domain with homology to the human CRAL/TRIO domain and yeast Sec14p 91 (Alonso et al., 2004, Gu et al., 1992, Zhang et al., 2012, Zhang e...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Dynamin2-py 125mentioning

confidence: 91%

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates

Chen

Yang

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…miR‐1 targets PTH and IL‐6 and it has crucial functions in the development and physiology of muscle tissue 36,37 ; one of his target is Dynamin3 , that is reported as the most downregulated gene in GSD‐osteoclasts array 15 . Dynamin 3 is an ubiquitin ligase that regulates microtubule dynamics and cell division 38 …”

Section: Discussionmentioning

confidence: 99%

Dysregulated miRNAs in bone cells of patients with Gorham‐Stout disease

et al. 2021

View full text Add to dashboard Cite

Gorham‐Stout disease (GSD) is a very rare disease characterized by increased bone erosion with angiomatous proliferation. The mechanisms underlying this disorder have not been deeply investigated. Due to its rarity, no guidelines are currently available for treatment and management of GSD. We recently evaluated the cellular alterations of the bone remodeling in patients showing that osteoclast precursors displayed increased ability to differentiate into osteoclasts and that affected osteoclasts resorb bone more actively than control cells. Moreover, osteoblasts isolated from a patient showed a defective ability to form mineralized nodules. In this paper, we investigated the molecular pathways involved in the cellular defects of GSD bone cells. For this study, we recruited nine patients and performed miRNome analysis of bone cells. Between the 178 miRNAs robustly expressed in GSD osteoclasts, significant modulation of three miRNAs (miR‐1246, miR‐1‐3p, and miR‐137‐3p) involved in the regulation of osteoclast formation and activity or in the angiomatous proliferation was found in patients' cells. Interestingly, miR‐1246 was also up‐regulated in serum exosomes from patients. Analysis of miRNAs from patient osteoblasts suggested alteration of miR‐204a‐5p, miR‐615‐3p and miR‐378a‐3p regulating osteoblast function and differentiation. The resulting miRNA pattern may help to understand better the mechanisms involved in GSD and to identify new potential therapeutic targets for this rare disease.

show abstract

“…Other studies indicated that members of the Dynamin family also function as molecular switches, similar to the classical signal GTPase [22]. A common feature of all dynamins and dynamin-related proteins is the presence of a GTPase effector domain (GED), a middle domain (MD), and a large N-terminal GTPase domain [23].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Analysis of Dynamin Gene Family in cassava (Manihot esculenta Crantz) and Transcriptional Regulation of Family Members ARC5 in Hormonal Treatments

Cao

Liu

Guo

et al. 2019

IJMS

View full text Add to dashboard Cite

The Dynamin gene family play a significance role in many physiological processes, especially ARC5 (Accumulation and replication of chloroplasts 5) in the process of plastid division. We performed a genome-wide analysis of the cassava Dynamin family based on the published cassava genome sequence and identified ARC5. 23 cassava Dynamins (MeDynamins) were identified and renamed. 23 MeDynamins were further divided into five major groups based on their structural and phylogenetic characteristics. The segmental duplication events have a significant impact on the expansion of MeDynamins. ARC5 expression analysis showed that there were differences between leaves and roots of cassava at different developmental stages. The tissue-specific expression analysis of the MeDynamins showed that most of MeDynamins were expressed in stem apical meristem and embryogenesis, whereas ARC5 was mainly expressed in leaves. The processing of IAA (Indole-3-acetic Acid) and MeJA (Methyl Jasmonate) verified the prediction results of cis-elements, and ACR5 was closely related to plant growth and positively correlated. It also indicated that high concentrations of MeJA treatment caused the cassava defense mechanism to function in advance. In conclusion, these findings provide basic insights for functional validation of the ARC5 genes in exogenous hormonal treatments.

show abstract

Regulation of dynamin family proteins by post-translational modifications

Cited by 17 publications

References 120 publications

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates

Dysregulated miRNAs in bone cells of patients with Gorham‐Stout disease

Genome-Wide Analysis of Dynamin Gene Family in cassava (Manihot esculenta Crantz) and Transcriptional Regulation of Family Members ARC5 in Hormonal Treatments

Contact Info

Product

Resources

About