V-type ATPases are capable of establishing a steep pH gradient across the membra
ID: 204718 • Letter: V
Question
V-type ATPases are capable of establishing a steep pH gradient across the membranes in which they are present. They are so called ‘V-type’ because they were originally identified as the culprit in acidification of plant Vacuoles. Establishment of a steep pH gradient also establishes a steep electrical gradient across that membrane. In biological situations, V-type ATPases are therefore often found in the same membranes as ion channels.
Osteoclasts are specialized bone macrophages that resorb bone. In the figure below, an osteoclast is depicted. Bone maintenance requires osteoclasts to resorb certain regions of bone so that osteoblasts can re-form the mineralized matrix in that same region. Osteoclasts are multinucleated cells that bind to bone and form a resorption lacuna, an extracellular lysosome of sorts with specialized proteases and phosphatases, that digests bone in an acidic compartment. The resorption lacuna is acidified by a V-type ATPase that moves protons across the osteoclast ruffled border membrane into the bone and allows for proteolytic digestion of bone. Note that an isozyme of carbonic anhydrase, carbonic anhydrase II (CAII), is expressed highly in osteoclasts. The ruffled border membrane contains a chloride channel (ClCN7) and a V-type ATPase (TCIRG1) which is capable of pumping protons. The basolateral membrane contains a chloride-bicarbonate exchanger, similar to red blood cells. Explain how these enzymes and transporters work in concert to acidify the resorption lacuna. Explain also why loss of function mutations in TCIRG1, ClCN7, or CAII all cause osteopetrosis, or ‘stone bones’.
Functional Secretory Domain Basolateral Domain CI HCO O CrRuffled Sealing Zone CI CIH ci O C CI cr O H Cr H* cr CI H CI Bone Resorption Lacunae (pH-4.5) D ,83 Integrin Acidified VesiclesNucleuso Proteolytic Encymes V-ATPase HCO/CI. Exchanger O Proteolytic EnzymesExplanation / Answer
The enzyme carbonic anhydrous is convert carbon dioxide into carbonic ions. The ruffled membrane contains a chloride channel (CICN7). It is an acid secreting domain of membrane which serves the acidification of bone lacuna. The vesicle ATPase or H+ V_ATPase (TCIRG1) along with chloride ion channel (which allows chloride ion to come in) create an acidic environment and induced resorption of lacuna.
If function of any of the gene CICN7, TCIRG1 or CAII may hinder in resorption of lacuna. If CICN7 is mutated than chloride ion channel is mis leaded, which results in uncontrolled movement of chloride ion across membrane. If TCIRG1 is mutated than H-ATPase can not provide H+ to inner matrix and acid is not formed. If gene CAII is mutated or function is loss, enzyme carbonic anhydrous maynot work properly. Loss of function mutation of any gene may result in abnormal or decrease resorption of lacuna and the condition is termed as osteopetrosis
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