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LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression.

Vaman V S A, Poppe H, Houben R, Grunewald TG, Goebeler M, Butt E - PLoS ONE (2015)

Bottom Line: In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell.Knockdown of LASP1 results in increased melanin concentration in the cells.Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg, Würzburg, Germany.

ABSTRACT
The LIM and SH3 protein 1 (LASP1) is a focal adhesion protein. Its expression is increased in many malignant tumors. However, little is known about the physiological role of the protein. In the present study, we investigated the expression and function of LASP1 in normal skin, melanocytic nevi and malignant melanoma. In normal skin, a distinct LASP1 expression is visible only in the basal epidermal layer while in nevi LASP1 protein is detected in all melanocytes. Melanoma exhibit no increase in LASP1 mRNA compared to normal skin. In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell. Knockdown of LASP1 results in increased melanin concentration in the cells. Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.

No MeSH data available.


Related in: MedlinePlus

Dynamin is a LASP1 binding partner.(A) Melanin concentration before and after LASP1 knockdown in MaMel2 cells. LASP1 knockdown efficiency was controlled by Western blot. Expression levels of tyrosinase and TRP1 are not affected. (B) Western blot analysis of dynamin, zyxin (positve control) and histone H2B (negative control), pulled-down with GST control beads and GST-LASP1 from MaMel2 and NHEM homogenate. (C) Western blot analysis of dynamin and LASP1 expression in melanoma cell lines and normal human epidermal melanocytes (NHEM). β-Actin served as loading control.
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pone.0129219.g004: Dynamin is a LASP1 binding partner.(A) Melanin concentration before and after LASP1 knockdown in MaMel2 cells. LASP1 knockdown efficiency was controlled by Western blot. Expression levels of tyrosinase and TRP1 are not affected. (B) Western blot analysis of dynamin, zyxin (positve control) and histone H2B (negative control), pulled-down with GST control beads and GST-LASP1 from MaMel2 and NHEM homogenate. (C) Western blot analysis of dynamin and LASP1 expression in melanoma cell lines and normal human epidermal melanocytes (NHEM). β-Actin served as loading control.

Mentions: As shown in Fig 1 LASP1 is highly expressed in melanocytic nevi, which are benign proliferations of melanin-producing melanocytes. Due to its domain structure, LASP1 can bind to several proteins involved in melanosome vesicle trafficking, e.g. F-actin [35, 36] and dynamin [10, 37]. We speculated whether LASP1 might have a specific function in melanocytes and therefore examined the melanin content of pigmented MaMel2 cells before and after LASP1 knockdown. As shown in Fig 4A, LASP1 silencing induced a moderate, but significant elevation of the melanin concentration in these cells (~10%, p = 0.03). Expression levels of tyrosinase and TRP1, two major players in melanogenesis, were not affected by LASP1 knockdown.


LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression.

Vaman V S A, Poppe H, Houben R, Grunewald TG, Goebeler M, Butt E - PLoS ONE (2015)

Dynamin is a LASP1 binding partner.(A) Melanin concentration before and after LASP1 knockdown in MaMel2 cells. LASP1 knockdown efficiency was controlled by Western blot. Expression levels of tyrosinase and TRP1 are not affected. (B) Western blot analysis of dynamin, zyxin (positve control) and histone H2B (negative control), pulled-down with GST control beads and GST-LASP1 from MaMel2 and NHEM homogenate. (C) Western blot analysis of dynamin and LASP1 expression in melanoma cell lines and normal human epidermal melanocytes (NHEM). β-Actin served as loading control.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4465371&req=5

pone.0129219.g004: Dynamin is a LASP1 binding partner.(A) Melanin concentration before and after LASP1 knockdown in MaMel2 cells. LASP1 knockdown efficiency was controlled by Western blot. Expression levels of tyrosinase and TRP1 are not affected. (B) Western blot analysis of dynamin, zyxin (positve control) and histone H2B (negative control), pulled-down with GST control beads and GST-LASP1 from MaMel2 and NHEM homogenate. (C) Western blot analysis of dynamin and LASP1 expression in melanoma cell lines and normal human epidermal melanocytes (NHEM). β-Actin served as loading control.
Mentions: As shown in Fig 1 LASP1 is highly expressed in melanocytic nevi, which are benign proliferations of melanin-producing melanocytes. Due to its domain structure, LASP1 can bind to several proteins involved in melanosome vesicle trafficking, e.g. F-actin [35, 36] and dynamin [10, 37]. We speculated whether LASP1 might have a specific function in melanocytes and therefore examined the melanin content of pigmented MaMel2 cells before and after LASP1 knockdown. As shown in Fig 4A, LASP1 silencing induced a moderate, but significant elevation of the melanin concentration in these cells (~10%, p = 0.03). Expression levels of tyrosinase and TRP1, two major players in melanogenesis, were not affected by LASP1 knockdown.

Bottom Line: In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell.Knockdown of LASP1 results in increased melanin concentration in the cells.Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg, Würzburg, Germany.

ABSTRACT
The LIM and SH3 protein 1 (LASP1) is a focal adhesion protein. Its expression is increased in many malignant tumors. However, little is known about the physiological role of the protein. In the present study, we investigated the expression and function of LASP1 in normal skin, melanocytic nevi and malignant melanoma. In normal skin, a distinct LASP1 expression is visible only in the basal epidermal layer while in nevi LASP1 protein is detected in all melanocytes. Melanoma exhibit no increase in LASP1 mRNA compared to normal skin. In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell. Knockdown of LASP1 results in increased melanin concentration in the cells. Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.

No MeSH data available.


Related in: MedlinePlus