Classical autophagy proteins LC3B and ATG4B facilitate melanosome movement on cytoskeletal tracks

Published on Aug 3, 2017in Autophagy11.059
· DOI :10.1080/15548627.2017.1327509
Amrita Ramkumar4
Estimated H-index: 4
(Institute of Genomics and Integrative Biology),
Divya Murthy6
Estimated H-index: 6
(Institute of Genomics and Integrative Biology)
+ 10 AuthorsRajesh S. Gokhale29
Estimated H-index: 29
(Institute of Genomics and Integrative Biology)
ABSTRACTMacroautophagy/autophagy is a dynamic and inducible catabolic process that responds to a variety of hormonal and environmental cues. Recent studies highlight the interplay of this central pathway in a variety of pathophysiological diseases. Although defective autophagy is implicated in melanocyte proliferation and pigmentary disorders, the mechanistic relationship between the 2 pathways has not been elucidated. In this study, we show that autophagic proteins LC3B and ATG4B mediate melanosome trafficking on cytoskeletal tracks. While studying melanogenesis, we observed spatial segregation of LC3B-labeled melanosomes with preferential absence at the dendritic ends of melanocytes. This LC3B labeling of melanosomes did not impact the steady-state levels of these organelles but instead facilitated their intracellular positioning. Melanosomes primarily traverse on microtubule and actin cytoskeletal tracks and our studies reveal that LC3B enables the assembly of microtubule translocon complex. At the mic...
  • References (94)
  • Citations (7)
#1Ashim Rai (TIFR: Tata Institute of Fundamental Research)H-Index: 6
#2Divya Pathak (TIFR: Tata Institute of Fundamental Research)H-Index: 3
Last. Roop Mallik (TIFR: Tata Institute of Fundamental Research)H-Index: 22
view all 6 authors...
Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule...
68 CitationsSource
#1Hana Popelka (UM: University of Michigan)H-Index: 9
#2Daniel J. Klionsky (UM: University of Michigan)H-Index: 117
The Atg8/LC3/GABARAP family of proteins, a group that has structural homology with ubiquitin, connects with a large set of binding partners to function in macroautophagy (hereafter autophagy). This interaction occurs primarily via a conserved motif termed the LC3-interacting region (LIR), or the Atg8-interacting motif (AIM). The consensus sequence for this motif, [W/F/Y]xx[L/I/V], can be found in many proteins, but only some of them are physiological partners containing a functional LIR/AIM. Bec...
19 CitationsSource
#1Morié IshidaH-Index: 6
#2Norihiko OhbayashiH-Index: 16
Last. Mitsunori FukudaH-Index: 69
view all 3 authors...
Rab1A regulates anterograde melanosome transport by recruiting kinesin-1 to melanosomes through interaction with SKIP
17 CitationsSource
#1Meng-meng Fu (UPenn: University of Pennsylvania)H-Index: 8
#2Erika L.F. Holzbaur (UPenn: University of Pennsylvania)H-Index: 69
Intracellular trafficking pathways, including endocytosis, autophagy, and secretion, rely on directed organelle transport driven by the opposing microtubule motor proteins kinesin and dynein. Precise spatial and temporal targeting of vesicles and organelles requires the integrated regulation of these opposing motors, which are often bound simultaneously to the same cargo. Recent progress demonstrates that organelle-associated scaffolding proteins, including Milton/TRAKs (trafficking kinesin-bind...
129 CitationsSource
Bidirectional movement by oppositely directed motors attached to the same cargo is frequently described as a 'tug of war'. However, some studies suggest that inhibiting one motor diminishes motility in both directions. To resolve this paradox, three bidirectional transport models, termed microtubule tethering, mechanical activation and steric disinhibition, are proposed, and a general mathematical modelling framework for bidirectional cargo transport is described.
178 CitationsSource
#1Xufeng Wu (NIH: National Institutes of Health)H-Index: 26
#2John A. Hammer (NIH: National Institutes of Health)H-Index: 51
The pigmentation of skin and hair in mammals is driven by the creation within melanocytes of melanosomes, a specialized pigment-producing organelle, and the subsequent intercellular transfer of this organelle to keratinocytes. This latter process is absolutely required for visible pigmentation and effective photo-protection because it serves to disperse the pigment in skin and hair. Therefore, the transfer of melanosomes from the melanocyte to the keratinocyte is as important for the biological ...
52 CitationsSource
#1Vivek T. NatarajanH-Index: 11
#2Parul GanjuH-Index: 5
Last. Rajesh S. GokhaleH-Index: 29
view all 5 authors...
The recurrent interaction of skin with sunlight is an intrinsic constituent of human life, and exhibits both beneficial and detrimental effects. The apparent robust architectural framework of skin conceals remarkable mechanisms that operate at the interface between the surface and environment. In this Review, we discuss three distinct protective mechanisms and response pathways that safeguard skin from deleterious effects of ultraviolet (UV) radiation. The unique stratified epithelial architectu...
79 CitationsSource
#1Meng-meng Fu (UPenn: University of Pennsylvania)H-Index: 8
#2Jeffrey J. Nirschl (UPenn: University of Pennsylvania)H-Index: 6
Last. Erika L.F. Holzbaur (UPenn: University of Pennsylvania)H-Index: 69
view all 3 authors...
Summary Autophagy is essential for maintaining cellular homeostasis in neurons, where autophagosomes undergo robust unidirectional retrograde transport along axons. We find that the motor scaffolding protein JIP1 binds directly to the autophagosome adaptor LC3 via a conserved LIR motif. This interaction is required for the initial exit of autophagosomes from the distal axon, for sustained retrograde transport along the midaxon, and for autophagosomal maturation in the proximal axon. JIP1 binds d...
100 CitationsSource
Selective autophagic degradation of cellular components underlies many of the important physiological and pathological implications that autophagy has for mammalian cells. Cytoplasmic vesicles, just like other intracellular items, can be subjected to conventional autophagic events where double-membrane autophagosomes specifically isolate and deliver them for lysosomal destruction. However, intracellular membranes appear to constitute common platforms for unconventional versions of the autophagic...
11 CitationsSource
#1Vivek T. Natarajan (IRI: Industrial Research Institute)H-Index: 11
#2Parul GanjuH-Index: 5
Last. Rajesh S. Gokhale (IRI: Industrial Research Institute)H-Index: 29
view all 14 authors...
Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigme...
39 CitationsSource
Cited By7
#1Aakansha Rai (AcSIR: Academy of Scientific and Innovative Research)
#2Barun Chatterjee (AcSIR: Academy of Scientific and Innovative Research)
Last. Soumya Sinha Roy (AcSIR: Academy of Scientific and Innovative Research)H-Index: 8
view all 5 authors...
Abstract The primary contributor for the determination of skin color is melanin, a pigment that is produced in specialized cells called melanocytes. At cellular level, melanin synthesis occurs through several enzymes like tyrosinase (TYR) and tyrosinase related proteins and the expression of these proteins are regulated transcriptionally by microphthalmia associated transcription factor (MITF). Melanin pigmentation is a complex process finely regulated by different transcription factors, structu...
#1Ruonan Zhang (MUST: Macau University of Science and Technology)H-Index: 3
#2Ting Pan (Hangzhou Normal University)H-Index: 1
Last. Xiaying Chen (Hangzhou Normal University)H-Index: 2
view all 27 authors...
Objective: Colorectal cancer is the third most common cancer worldwide and the second most common cancer cause of death worldwide. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. β-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the...
#1Kun Wang (NCU: Nanchang University)H-Index: 1
#2Shengjia Peng (NCU: Nanchang University)
Last. Qiren Huang (NCU: Nanchang University)H-Index: 15
view all 8 authors...
Abstract As a flavonoid, naringin (Nar) has been shown to have multiple pharmacological effects including lowering blood cholesterol, reducing thrombus formation and improving microcirculation. However, effects of Nar on function and autophagy of vascular endothelial cells under high glucose and high fat (HG/HF) stress are largely unclear. This study was designed to investigate such effects of Nar in human umbilical vein endothelial cells (HUVECs) and to determine whether such effects are relate...
#1Shuang Lei (PRC: China Medical University (PRC))H-Index: 1
#2Xue-Mei Liu (PRC: China Medical University (PRC))H-Index: 2
Last. Xu Chen (PRC: China Medical University (PRC))H-Index: 3
view all 6 authors...
Abstract Introduction The dentinogenesis potential of stem cells during dentin-pulp tissue regeneration may be compromised by microorganism components. Here we aimed to investigate the cell viability and osteo-/odontogenic differentiation of stem cells from apical papilla (SCAP) exposed to bacterial lipopolysaccharide (LPS) and to evaluate the molecular mechanism in vitro. Methods CCK8 assay was used to assess the SCAP proliferation rate on exposure to different concentrations of LPS in medium. ...
1 CitationsSource
#1Li Yan (Peking Union Medical College)H-Index: 9
#1Li Yan (Peking Union Medical College)H-Index: 3
Last. Yuan-Bo Liu (Peking Union Medical College)H-Index: 2
view all 10 authors...
Electron beam (EB) irradiation is useful to reduce the recurrence of keloids; however, the underlying mechanism remains unknown. MicroRNA-21 (miR-21), which regulates autophagy during cancer radiation therapy, was identified as a potential therapeutic target for keloids. Here, we investigate the regulatory mechanism(s) of miR-21-5p on keloid fibroblast autophagy and migration after EB irradiation. The microRNA expression profile of the keloid dermis was examined by performing a microRNA microarr...
1 CitationsSource
#1Lynn Petukhova (Columbia University)H-Index: 20
#2Aakash V. Patel (Columbia University)H-Index: 1
Last. Angela M. Christiano (Columbia University)H-Index: 58
view all 11 authors...
: Alopecia areata (AA) is a highly prevalent autoimmune disease that attacks the hair follicle and leads to hair loss that can range from small patches to complete loss of scalp and body hair. Our previous linkage and genome-wide association studies (GWAS) generated strong evidence for aetiological contributions from inherited genetic variants at different population frequencies, including both rare mutations and common polymorphisms. Additionally, we conducted gene expression (GE) studies on sc...
1 CitationsSource
#1Chen-Meng Qiao (Jiangnan University)H-Index: 2
#2Meng-Fei Sun (Jiangnan University)H-Index: 4
Last. Yan-Qin Shen (Jiangnan University)H-Index: 13
view all 9 authors...
Abstract Aggregation of α-Synuclein is central to the pathogenesis of Parkinson's disease (PD). However, these α-Synuclein inclusions are not only present in brain, but also in gut. Enteroendocrine cells (EECs), which are directly exposed to the gut lumen, can express α-Synuclein and directly connect to α-Synuclein-containing nerves. Dysbiosis of gut microbiota and microbial metabolite short-chain fatty acids (SCFAs) has been implicated as a driver for PD. Butyrate is an SCFA produced by the gut...
#1Radhika Gupta (DU: University of Delhi)H-Index: 8
Last. Kangana Malhotra (DU: University of Delhi)
view all 5 authors...
#1Dandan Liu (NAU: Nanjing Agricultural University)H-Index: 8
#2Lei Ge (NAU: Nanjing Agricultural University)
Last. Kehe Huang (NAU: Nanjing Agricultural University)H-Index: 23
view all 7 authors...
Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogenic virus that causes severe diarrhea and dehydration in pigs of all ages. Deoxynivalenol (DON), the most abundant trichothecene in food and feed, causes vomit and diarrhea in animals and human. However, whether DON exposure could affect PEDV infection remains unknown. Herein, we investigated the impacts of DON on entry and replication of PEDV, morbidity situation of piglets and the mechanisms involved. In vivo, twenty-seven pi...
#1Yin Pan (Nanjing Medical University)H-Index: 3
#2Zehan Li (Nanjing Medical University)H-Index: 4
Last. Jinhua Yu (Nanjing Medical University)H-Index: 24
view all 7 authors...
: Fluoride (sodium fluoride) is thought to be essential in the development of tooth, and research shows that fluoride can modulate the differentiation of dental stem cells. However, the effects of fluoride on the committed differentiation of stem cells from apical papilla (SCAPs) and the underlying mechanisms remain unclear. Here, SCAPs were isolated from healthy extracted human third molars with immature roots and then were cultured with NaF conditioned media. Cell Counting Kit-8, EdU staining,...
3 CitationsSource