IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation

Natarajan, Vivek T.; Ganju, Parul; Singh, Archana; Vijayan, Vinaya; Kirty, Kritika; Yadav, Shalini; Puntambekar, Shraddha; Bajaj, Sonali; Dani, Prachi P.; Kar, Hemanta Kumar; Gadgil, Chetan; Natarajan, Krishnamurthy; Rani, Rajni; Gokhale, Rajesh S.

doi:10.1073/pnas.1304988111

Cited by 94 publications

(119 citation statements)

References 36 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…IFN-γ-induced these changes in melanogenesis are reversible. 19) In our study, the results was consistent with the data report, comparing the first column with the second column in Figs. 5A Figs.…”

Section: Discussionsupporting

confidence: 93%

“…19) Primary human melanocytes were treated with IFN-γ for 7 d and then allowed to recover for 5 d (day 12) by fresh medium without IFN-γ, the pigmentation process reinitiated. In accordance with those reported in the previous papers, our results also demonstrated that the inhibition of IFN-γ was reversible after the removal of IFN-γ, as shown in the second columns of Figs.…”

Section: Effect Of Cross-talk Between 5-ht and Ifn-γ On Nhem Was Irrementioning

confidence: 99%

See 1 more Smart Citation

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

Zhou

Ling

Ping

2016

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Interferon-γ (IFN-γKey words interferon-γ (IFN-γ); 5-hydroxytryptamine (5-HT); cross-talk; melanogenesis; migration Skin is the largest organ in human body, which plays a role as biologically active barrier to the external environment. It acts not only as a target for neuroendocrine signals but also a source of hormones and neurotransmitters, particularly the epidermis.1) Epidermis and dermis are the two main parts of skin. Epidermal melanocytes, derived from the neural crest, can produce melanin to absorb ultraviolet radiation and provide photoprotection.2) Melanin is synthesized in melanosomes, which are specialized lysosomerelated organelle (LRO) of pigment cells devoting to the biosynthesis, storage and transport of melanin.3) Melanosomes undergo 4 maturation stages, each characterized by unique ultrastructural morphology and melanin content. 4,5) The principal role of the melanocyte is to produce the pigment within melanosomes and to transfer these organelles to upwards of 40 keratinocytes, which are neighboring melanocyte to constitute the 'epidermal melanin unit.' Melanocyte transport melanosomes from the formation site in the cell center to the principal site of transfer at dendritic tips. Accomplishing this feat, melanocyte needs to couple long-range, bidirectional microtubule-dependent transport of melanosomes along the length of dendrites with the capture and local movement of the organelles in actin-rich dendritic tips by the actin-based motor protein myosin Va. 5,6) Studies have shown that there are four possible mechanisms described for melanosome transfer, including the cytophagocytosis model, membrane fusion model, shedding-phagocytosis model and exocytosis-endocytosis model. 6) In addition, multifarious signaling pathways and transcription factors firmly manage melanocyte migration. These proteins and pathways provide and integrate signals to create the proper environment for its normal development and migration. 2)Melanin biosynthesis process is under a complex control mediated by multiple elements through different pathways. A series of pigment cell-specific melanosomal proteins are responsible for melanogenesis, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT). 7-9) Skin cells can produce hormones, neurotransmitters and neuropeptides and corresponding functional receptors, owing to which constitute the cutaneous equivalent of the hypothalamic-pituitary-adrenal (HPA) axis.10,11) It has recently uncovered that cutaneous expression of the biochemical machinery involved in the sequential transformation of L-tryptophan to serotonin and melatonin. 12,13) Serotonin 5-hydroxytryptamine (5-HT) is a neurotransmitter whose actions are mediated via an interaction with receptors, including seven families (5-HT 1-7 receptors) with at least 21 subtypes. Skin cells express mRNA encoding 5-HT receptors, 5-HT 1A, -1B, -2A, -2B, -2C, and -7 receptor.14,15) 5-HT 2A receptor was reported participating in the regulatory processes of 5-HT on melanogenesis.16) Our preli...

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Effect Of Cross-talk Between 5-ht and Ifn-γ On Nhem Was Irrementioning

confidence: 99%

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

Zhou

Ling

Ping

2016

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…After parsing the motifs against the known TF binding sites in vertebrates, we compiled lists of top potential TFs binding to each motif (Table S2). We then analysed the expression of six of the TFs, which were predicted by all of the three motif enrichment tools and implicated in pigmentation processes (Barrallo-Gimeno et al, 2004; Cook & Sturm, 2008; Li et al, 2009; Agarwal et al, 2011; Besch & Berking, 2014; Natarajan et al, 2014) (Fig. 4).…”

Section: Resultsmentioning

confidence: 99%

A gene expression study of dorso-ventrally restricted pigment pattern in adult fins ofNeolamprologus meeli, an African cichlid species

Ahi

Sefc

2017

PeerJ

View full text Add to dashboard Cite

Fish color patterns are among the most diverse phenotypic traits found in the animal kingdom. Understanding the molecular and cellular mechanisms that control in chromatophore distribution and pigmentation underlying this diversity is a major goal in developmental and evolutionary biology, which has predominantly been pursued in the zebrafish model system. Here, we apply results from zebrafish work to study a naturally occurring color pattern phenotype in the fins of an African cichlid species from Lake Tanganyika. The cichlid fish Neolamprologus meeli displays a distinct dorsal color pattern, with black and white stripes along the edges of the dorsal fin and of the dorsal half of the caudal fin, corresponding with differences in melanophore density. To elucidate the molecular mechanisms controlling the differences in dorsal and ventral color patterning in the fins, we quantitatively assessed the expression of 15 candidate target genes involved in adult zebrafish pigmentation and stripe formation. For reference gene validation, we screened the expression stability of seven widely expressed genes across the investigated tissue samples and identified tbp as appropriate reference. Relative expression levels of the candidate target genes were compared between the dorsal, striped fin regions and the corresponding uniform, grey-colored regions in the anal and ventral caudal fin. Dorso-ventral expression differences, with elevated levels in both white and black stripes, were observed in two genes, the melanosome protein coding gene pmel and in igsf11, which affects melanophore adhesion, migration and survival. Next, we predicted potential shared upstream regulators of pmel and igsf11. Testing the expression patterns of six predicted transcriptions factors revealed dorso-ventral expression difference of irf1 and significant, negative expression correlation of irf1 with both pmel and igsf11. Based on these results, we propose pmel, igsf11 and irf1 as likely components of the genetic mechanism controlling distinct dorso-ventral color patterns in N. meeli fins.

show abstract

“…Moreover, Natarajan et al indicated a regulatory role of IFN-γ in skin pigmentation. They showed that IFN-γ signaling impedes maturation of the melanosome, which is a major site for synthesis and storage of melanine (7). Altogether, the actual mechanism of melanocytes killing in the skin of patients with vitiligo has not been definitively determined.…”

Section: Dear Editormentioning

confidence: 99%

IFN-γ Promotes Apoptosis of Melanocytes in Vitiligo

Jadali

2015

J Skin Stem Cell

View full text Add to dashboard Cite

IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation

Cited by 94 publications

References 36 publications

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

A gene expression study of dorso-ventrally restricted pigment pattern in adult fins ofNeolamprologus meeli, an African cichlid species

IFN-γ Promotes Apoptosis of Melanocytes in Vitiligo

Contact Info

Product

Resources

About