Patched
Encyclopedia
Patched is a conserved 12-pass transmembrane protein receptor that plays an obligate negative regulatory role in the Hedgehog signaling pathway
Hedgehog signaling pathway
In a growing embryo, cells develop differently in the head or tail end of the embryo, the left or right, and other positions. They also form segments which develop into different body parts. The hedgehog signaling pathway gives cells information that they need to make the embryo develop properly....

 in insects and vertebrates. The original mutations in the ptc gene were discovered in the fruit fly Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

 by 1995 Nobel Laureates Eric F. Wieschaus
Eric F. Wieschaus
-External links:***, excellent profile**...

 and Christiane Nusslein-Volhard
Christiane Nüsslein-Volhard
Christiane Nüsslein-Volhard is a German biologist who won the Albert Lasker Award for Basic Medical Research in 1991 and the Nobel Prize in Physiology or Medicine in 1995, together with Eric Wieschaus and Edward B...

 and colleagues, and the gene was independently cloned in 1989 by Joan Hooper in the laboratory of Matthew P. Scott
Matthew P. Scott
Matthew P. Scott is a developmental biologist and HHMI investigator at Stanford University studying how embryonic and later development is governed by proteins that control gene activity and cell signaling processes....

, and by Philip Ingham and colleagues. Patched is an embryo-lethal segment polarity gene
Segment polarity gene
A segmentation gene is a generic term for a gene whose function is to specify tissue pattern in each repeated unit of a segmented organism. In the fruit fly Drosophila melanogaster, segment polarity genes help to define the anterior and posterior polarities within each embryonic parasegment by...

 that is important for proper segmentation
Segmentation
Segmentation may mean:*Market segmentation, in economics and marketingBiology*A process of morphogenesis that divides a metazoan body into a series of semi-repetitive segments*Segmentation , a series of semi-repetitive segments...

 in the fly embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...

. Patched controls the spatial distribution of Hedgehog protein in part via endocytosis of bound hedgehog protein, which is then targeted for lysosomal degradation.

Role in presence and absence of Hedgehog Signaling

Patched is part of a negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

 mechanism for Hedgehog signaling that helps shape the spatial gradient of signaling activity across tissues. In the absence of hedgehog, low levels of patched are sufficient to suppress activity of the signal transduction pathway. When Hedgehog is present and binds to Patched, Patched somehow inhibits the activity of Smoothened
Smoothened
Smoothened is a G protein-coupled receptor protein encoded by the gene of the hedgehog pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine....

, a G coupled protein receptor most of which is stored in membrane bound vesicles internally within the cell and which increases at the cell surface when Hedgehog is present. Smoothened must be present on the cell membrane in order for the Hedgehog signaling pathway to be activated. Among other genes, the transcription of the patched gene is induced by Hedgehog signaling, with the accumulation of the Patched protein limiting signaling through the Smoothened protein. Recent work implicates the cilium
Cilium
A cilium is an organelle found in eukaryotic cells. Cilia are slender protuberances that project from the much larger cell body....

 in intracellular trafficking of Hedgehog signaling components in vertebrate cells.

Role in Disease

Mutated patched proteins have been implicated in a number of cancers including Basal Cell Carcinoma
Basal cell carcinoma
Basal-cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant. Statistically, approximately 3 out of 10 Caucasians may develop a...

, Medulloblastoma
Medulloblastoma
Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa.Previously, medulloblastomas were thought to represent a subset of primitive neuroectodermal tumor of the posterior fossa...

, and Rhabdomyosarcoma
Rhabdomyosarcoma
A rhabdomyosarcoma is a type of cancer, specifically a sarcoma , in which the cancer cells are thought to arise from skeletal muscle progenitors. It can also be found attached to muscle tissue, wrapped around intestines, or in any anatomic location...

.. Hereditary mutations in the human patched homolog PTCH1
PTCH1
Protein patched homolog 1 is a protein that is the member of the Patched family and in humans is encoded by the PTCH1 gene.- Function :PTCH1 is a member of the patched gene family and is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in...

 cause autosomal dominant Gorlin syndrome, which consists of overgrowth and hereditary disposition to cancer including basal cell carcinoma and medulloblastoma. Mice with mutations in mouse PTCH1 develop medulloblastoma
Medulloblastoma
Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa.Previously, medulloblastomas were thought to represent a subset of primitive neuroectodermal tumor of the posterior fossa...

.
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