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. Author manuscript; available in PMC: 2009 Oct 1.
Published in final edited form as: Annu Rev Genomics Hum Genet. 2008;9:359–386. doi: 10.1146/annurev.genom.9.081307.164303

Figure 8. Distribution of melanogenic proteins TYRP1, TYR1 and PMEL17 in melanocytes of patients with LRO disorders.

Figure 8

Confocal immunofluorescence microscopy of primary epidermal melanocytes derived from a normally pigmented individual and patients with LRO biogenesis defects stained for (a–e) TYRP1 (anti-mouse MEL5), (f–j) TYR (anti-mouse Tyrosinase), and (k–o) PMEL17 (anti-mouse HMB45). All melanocytes were co-stained with TO-PRO-3 to visualize the nucleus.

(a,f,k) Normal melanocytes demonstrate punctuate (a) TYRP1, (f) TYR and (k) PMEL17 staining in the perinuclear region and throughout the dendrites with TYRP1 and TYR accumulation in the dendritic tips.

(b,g,l) BLOC-2 deficient melanocytes were derived from an HPS-5 patient compound heterozygous for a nonsense mutation (c.2624C>T; p.R865X) and a one base pair deletion (c.2264delT: P.L875fsX19) in exon 18 of HPS5. BLOC-2 deficient melanocytes display punctate staining of (b) TYRP1 and (g) TYR in the perinuclear region extending into the dendrites, but lack pronounced accumulation of TYRP1 and TYR in the tips. (l) PMEL17 staining in BLOC-2 deficient melanocytes is distributed throughout the cell as in normal melanocytes.

(c,h,m) BLOC-3 deficient melanocytes were derived from an HPS-1 patient homozygous for a 16 base-pair duplication (c.1472_1487dup16) in exon 15 of HPS1. In the absence of BLOC-3 (c) TYRP1 and (h) TYR are concentrated in the perinuclear/TGN region while (m) PMEL17 extends into the dendrites and appears normally distributed.

(d,i,n) GS2 melanocytes were derived from a patient compound heterozygous for two nonsense mutations (c.550C>T; p.R184X and c.598C>T; p.R200X) in Rab27A. In GS2 melanocytes, (d) TYRP1, (i) TYR, and (n) PMEL17 localize to the perinuclear area and do not occupy the dendritic tips.

(e,j,o) CHS melanocytes were derived from a patient carrying a nonsense mutation (c.1540C>T; p.R514X) in exon 5 and a one base pair deletion (c.9893delT; p.F3298fsX3304) in exon 43 in CHS1. In CHS melanocytes, (e) TYRP1 localizes to vesicular structures in the perinuclear area with some dendritic localization, (j) TYR accumulates in large granules that localize to the dendrites but not their tips, and (o) PMEL17 localizes to enlarged vesicular structures that are present in the perinuclear and dendritic area but not in the dendritic tips. All images are 1D projections of confocal z-sections. Scale bars = 10 μm.