Filopodia are conduits for melanosome transfer to keratinocytes

Abstract

Melanosomes are specialized melanin-synthesizing organelles critical for photoprotection in the skin. Melanosome transfer to keratinocytes, which involves whole organelle donation to another cell, is a unique biological process and is poorly understood. Time-lapse digital movies and electron microscopy show that filopodia from melanocyte dendrites serve as conduits for melanosome transfer to keratinocytes. Cdc42, a small GTP-binding protein, is known to mediate filopodia formation. Melanosome-enriched fractions isolated from human melanocytes expressed the Cdc42 effector proteins PAK1 and N-WASP by western blotting. Expression of constitutively active Cdc42(Cdc42V12) in melanocytes co-cultured with keratinocytes induced a highly dendritic phenotype with extensive contacts between melanocytes and keratinocytes through filopodia, many of which contained melanosomes. These results suggest a unique role for filopodia in organelle transport and, in combination with our previous work showing the presence of SNARE proteins and rab3a on melanosomes, suggest a novel model system for melanosome transfer to keratinocytes.

Polyplexes Are Endocytosed by and Trafficked within Filopodia

“…These structures are denoted in various studies under differing names such as nanotubes, tunneling nanotubes (TNT), , filopodial bridges, and cytonemes . These structures have been found to traffic viruses, , organelles, proteins, , and nanocomplexes (i.e., lipoplexes and polyplexes) from one cell to another cell. The trafficking mechanism along these filopodial conduits has been proposed to take place either along the outer surface ,,, or inside ,,,, of these structures.…”

Proteomic Analysis of Early Melanosomes: Identification of Novel Melanosomal Proteins

“…Even though active melanogenic enzymes are found in the sorting vesicles and can be detected in stage I melanosomes, melanin synthesis does not begin until after gp100 is processed from its membrane bound into its soluble form and is integrated into the fibrillar matrix characteristic of stage II melanosomes. , Stage III and IV melanosomes are mature forms that are laden with increasing amounts of dark melanin pigment. As the pigment is synthesized and deposited on the melanosome fibrils, the melanosomes move from the perinuclear region toward the periphery of the melanocytes, i.e., the dendrite tips. , This intracellular movement of melanosomes is mediated in part by microtubular motor myosin Va that is recruited by rab27a via its interaction with melanophilin, a process that is only now being clarified at the molecular level. − Once they arrive at the dendritic tips, melanosomes are captured by actin filaments and are transferred to adjoining keratinocytes. , …”

“…[10][11][12] Once they arrive at the dendritic tips, melanosomes are captured by actin filaments and are transferred to adjoining keratinocytes. 9,13 Despite the cloning and characterization of several key structural and enzymatic proteins that make up these organelles, the mechanisms involved in the biogenesis of melanosomes, the regulation of melanin biosynthesis and their transfer to keratinocytes are still only partially understood. The presence of melanosomes uniquely in melanocytes does not reveal whether they are generated by a novel or an existing cellular mechanism for organelle biogenesis.…”

Mimicking Melanosomes: Polydopamine Nanoparticles as Artificial Microparasols

“…39,40 In epidermal melanocytes, melanosomes are ultimately transported to neighboring keratinocytes, which retain the melanin while in the basal layer and degrade as they move to the skin surface and differentiate. 41 The melanosome is characterized as a lysosomerelated organelle because melanin must be synthesized and polymerized with the help of enzymes and structural proteins within the organelle, where acidic pH seems to be required. 42,43 We hypothesized that the transportation and degradation of MelNPs were similarly driven by a lysosomal process in HEKa cells.…”