Understanding Hair Transplants and Hair Loss - Pacific Hair

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Understanding Hair Transplants and Hair Loss - Pacific Hair

transmembrane segments, 5 of which are homologous to a conserved region that has

been identified in several proteins involved in cholesterol homeostasis and has been

designated the sterol-sensing domain (SSD). In the present study, we show that a Ptc

mutant with a single amino acid substitution in the SSD induces target gene activation

in a ligand-independent manner . This mutant Ptc(SSD) protein shows dominant-negative

activity in blocking Hh signaling by preventing the downregulation of Smoothened

(Smo), a positive effector of the Hh pathway . Despite its dominant-negative activity, the

mutant Ptc protein functioned like the wild-type protein in sequestering and internalizing

Hh. In addition, we show that Ptc(SSD) preferentially accumulates in endosomes of the

endocytic compartment . All these results suggest a role of the SSD of Ptc in mediating

the vesicular trafficking of Ptc to regulate Smo activity.” Strutt et al., MRC Intercellular

Signaling Group, Centre for Developmental Genetics, Department of Biomedical Science,

University of Sheffield, Sheffield, United Kingdom, “The tumor suppressor gene

patched (ptc) encodes an approximately 140 kDa polytopic transmembrane protein

that binds members of the Hedgehog (Hh) family of signaling proteins and regulates

the activity of Smoothened (Smo), a G protein-coupled receptor-like protein essential

for Hh signal transduction . Ptc contains a sterol-sensing domain (SSD), a motif found

in proteins implicated in the intracellular trafficking of cholesterol, and/or other cargoes.

Cholesterol plays a critical role in Hedgehog (Hh) signaling by facilitating the regulated

secretion and sequestration of the Hh protein, to which it is covalently coupled. In addition,

cholesterol synthesis inhibitors block the ability of cells to respond to Hh, and this

finding points to an additional requirement for the lipid in regulating downstream components

of the Hh signaling pathway . Although the SSD of Ptc has been linked to both the

sequestration of, an the cellular response to Hh, definitive evidence for its function has

so far been lacking. Here we describe the identification and characterization of two missense

mutations in the SSD of Drosophila Ptc; strikingly, while both mutations abolish

Smo repression, neither affects the ability of Ptc to interact with Hh . We speculate that

Ptc may control Smo activity by regulating an intracellular trafficking process dependent

upon the integrity of the SSD .

In Vitro Growth of Hair Follicle Cells

Mass-Szabowski et al ., (2001), reported that organotypic cocultures of keratinocytes

and fibroblasts generate normal epithelial cells. These results were obtained with fibroblasts

from any species of any tissue type . Further, they report that the “use of mouse

fibroblasts and human keratinocytes facilitates the identification of the origin of compounds

involved in epidermal tissue reconstitution and growth regulation . Moreover, the

U n d e r s t a n d i n g H a i r T r a n s p l a n t s a n d H a i r L o s s

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