A Role of Phosphatidylserine in the Function of Recycling Endosomes

Cells internalize proteins and lipids in the plasma membrane (PM) and solutes in the extracellular space by endocytosis. The removal of PM by endocytosis is constantly balanced by the replenishment of proteins and lipids to PM through recycling pathway. Recycling endosomes (REs) are specific subsets of endosomes. Besides the established role of REs in recycling pathway, recent studies have revealed unanticipated roles of REs in membrane traffic and cell signalling. In this review, we highlight these emerging issues, with a particular focus on phosphatidylserine (PS), a phospholipid that is highly enriched in the cytosolic leaflet of RE membranes. We also discuss the pathogenesis of Hermansky Pudlak syndrome type 2 (HPS2) that arises from mutations in the AP3B1 gene, from the point of view of dysregulated RE functions.

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AP-3 Mediates Tyrosinase but Not TRP-1 Trafficking in Human Melanocytes

Molecular Biology of the Cell ◽

10.1091/mbc.12.7.2075 ◽

2001 ◽

Vol 12 (7) ◽

pp. 2075-2085 ◽

Cited By ~ 101

Author(s):

Marjan Huizing ◽

Rangaprasad Sarangarajan ◽

Erin Strovel ◽

Yang Zhao ◽

William A. Gahl ◽

...

Keyword(s):

Dense Body ◽

Multivesicular Bodies ◽

Normal Pattern ◽

Late Endosomes ◽

Human Melanocytes ◽

Hermansky Pudlak Syndrome ◽

Functional Deficiency ◽

Tyrosinase Related Protein

Patients with Hermansky-Pudlak syndrome type 2 (HPS-2) have mutations in the β3A subunit of adaptor complex-3 (AP-3) and functional deficiency of this complex. AP-3 serves as a coat protein in the formation of new vesicles, including, apparently, the platelet's dense body and the melanocyte's melanosome. We used HPS-2 melanocytes in culture to determine the role of AP-3 in the trafficking of the melanogenic proteins tyrosinase and tyrosinase-related protein-1 (TRP-1). TRP-1 displayed a typical melanosomal pattern in both normal and HPS-2 melanocytes. In contrast, tyrosinase exhibited a melanosomal (i.e., perinuclear and dendritic) pattern in normal cells but only a perinuclear pattern in the HPS-2 melanocytes. In addition, tyrosinase exhibited a normal pattern of expression in HPS-2 melanocytes transfected with a cDNA encoding the β3A subunit of the AP-3 complex. This suggests a role for AP-3 in the normal trafficking of tyrosinase to premelanosomes, consistent with the presence of a dileucine recognition signal in the C-terminal portion of the tyrosinase molecule. In the AP-3–deficient cells, tyrosinase was also present in structures resembling late endosomes or multivesicular bodies; these vesicles contained exvaginations devoid of tyrosinase. This suggests that, under normal circumstances, AP-3 may act on multivesicular bodies to form tyrosinase-containing vesicles destined to fuse with premelanosomes. Finally, our studies demonstrate that tyrosinase and TRP-1 use different mechanisms to reach their premelanosomal destination.

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In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids

Stem Cell Reports ◽

10.1016/j.stemcr.2019.01.014 ◽

2019 ◽

Vol 12 (3) ◽

pp. 431-440 ◽

Cited By ~ 20

Author(s):

Yohei Korogi ◽

Shimpei Gotoh ◽

Satoshi Ikeo ◽

Yuki Yamamoto ◽

Naoyuki Sone ◽

...

Keyword(s):

Stem Cell ◽

Pluripotent Stem Cell ◽

Disease Modeling ◽

Induced Pluripotent Stem Cell ◽

Syndrome Type ◽

Hermansky Pudlak Syndrome ◽

Induced Pluripotent

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Disruption of AP3B1by a chromosome 5 inversion: a new disease mechanism in Hermansky-Pudlak syndrome type 2

BMC Medical Genetics ◽

10.1186/1471-2350-14-42 ◽

2013 ◽

Vol 14 (1) ◽

Cited By ~ 15

Author(s):

Matthew L Jones ◽

Sherina L Murden ◽

Claire Brooks ◽

Viv Maloney ◽

Richard A Manning ◽

...

Keyword(s):

Syndrome Type ◽

New Disease ◽

Chromosome 5 ◽

Disease Mechanism ◽

Hermansky Pudlak Syndrome

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Novel AP3B1 compound heterozygous mutations in a Japanese patient with Hermansky–Pudlak syndrome type 2

The Journal of Dermatology ◽

10.1111/1346-8138.15177 ◽

2019 ◽

Vol 47 (2) ◽

pp. 185-189 ◽

Cited By ~ 3

Author(s):

Takuro Nishikawa ◽

Ken Okamura ◽

Mizuki Moriyama ◽

Kenji Watanabe ◽

Atsuko Ibusuki ◽

...

Keyword(s):

Japanese Patient ◽

Compound Heterozygous ◽

Syndrome Type ◽

Hermansky Pudlak Syndrome ◽

Compound Heterozygous Mutations

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Nutrology and type 2 diabetes: Nutrient pathophysiology and the transition from health to disease

International Journal of Nutrology ◽

10.1055/s-0040-1701422 ◽

2012 ◽

Vol 05 (01) ◽

pp. 006-013 ◽

Cited By ~ 1

Author(s):

Eugenio Cersosimo ◽

José Eduardo Dutra de Oliveira

Keyword(s):

Type 2 Diabetes ◽

Genetic Factors ◽

Close Association ◽

Point Of View ◽

Dietary Recommendations ◽

Body Distribution ◽

Adverse Environmental Conditions ◽

Molecular Aspects

ABSTRACTFrom a Nutrology point of view, type 2 diabetes is a multi-factorial form of clinical “malnutrition” resulting from the intake of an imbalanced diet in combination with adverse environmental conditions and in the presence of predisposing genetic factors. In this review article, we present evidence of a close association between clinical obesity in a specific genetic background as the pillars of the process underlying the development of type 2 diabetes. We review the basics of the energy balance and the role of fat storage and body distribution in the pathogenesis of insulin resistance. We describe some molecular aspects of nutrients under normal physiology and during the metabolic and hormonal abnormalities that accompany type 2 diabetes. We conclude with a brief discussion of the principles behind popular dietary recommendations aimed at preventing the full development of diabetes mellitus and its complications.

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Cardio‐Renal Syndrome Type 2: The Role of the Cardiac Spinal Afferent Reflex

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.564.3 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Zhiqiu Xia ◽

Li Han ◽

Alicia Schiller ◽

Peter R. Pellegrino ◽

Steven J. Lisco ◽

...

Keyword(s):

Syndrome Type

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Primary immunodeficiency associated with hypopigmentation: A differential diagnosis approach

Allergologia et Immunopathologia ◽

10.15586/aei.v49i2.61 ◽

2021 ◽

Vol 49 (2) ◽

pp. 178-190

Author(s):

Raha Zamani ◽

Sepideh Shahkarami ◽

Nima Rezaei

Keyword(s):

Primary Immunodeficiency ◽

Treatment Options ◽

Genetic Diseases ◽

Endosomal Trafficking ◽

Syndrome Type ◽

Griscelli Syndrome ◽

Hermansky Pudlak Syndrome ◽

Chediak Higashi Syndrome ◽

Prompt Diagnosis

Primary immunodeficiency diseases (PIDs) are a group of more than 400 disorders representing aberrant functioning or development of immune system. Hypopigmentation syndromes also characterize a distinguished cluster of diseases. However, hypopigmentation may also signify a feature of genetic diseases associated with immunodeficiency, such as Chediak–Higashi syndrome, Griscelli syndrome type 2, Hermansky–Pudlak syndrome type 2 and type 10, Vici syndrome, and P14/LAMTOR2 deficiency, all of which are linked with dysfunction in vesicular/endosomal trafficking. Regarding the highly overlapping features, these disorders need a comprehensive examination for prompt diagnosis and effective management. As an aid to clinician, distinguishing the pathophysiology, clinical phenotype, and diagnosis as well as treatment options of the six mentioned PID disorders associated with hypopigmentation are described and discussed in this review.

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