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Intracellular Compartments and Protein Sorting

Date: 12. April 2018

Signal for Transport of Proteins
Sqadia video is the demonstration of Intracellular Compartments and Protein Sorting. The central dogma of molecular biology describes the two-step process, transcription and translation, by which the information in genes flows into proteins. Proteins carry signal sequence/patch for their transport from cytoplasm to ER and from ER to Golgi and other organelles. Intracellular Secretory pathway leads outward from ER towards the Golgi Apparatus and Cell Surface, with a side route leading to lysosomes. Transport Vesicle bud off from one compartment and fuse with another. In doing so they carry material as cargo from the lumen and membrane of donor compartment to the lumen and membrane of the target compartment. Three well characterized coated Vesicles that differ in coat proteins are Clathrin Coated Vesicles, COP1 Coated Vesicles, and COP2 Coated Vesicles. Each type is used in different step in cell.

Types of Coated Vesicles
The major component of Clathrin Coated vesicles is Clathrin itself. Each Clathrin subunit consists of 3 large and 3 small Polypeptide chains that together form a three legged structure called Triskelion. Second Major protein is Adaptin, which is required both to bind the Clathrin coat to the membrane and to trap various transmembrane protein including transmembrane receptors. Dynamin regulated the pinching off from the membrane. In Pinching off process, the 2 leaflets of membrane are brought into close proximity and fuse, sealing off the forming vesicle. Once vesicle is released from the membrane the Clathrin Coat is rapidly lost. A chaperone protein hsp 70 family function as uncoating ATPases, using the energy of ATP hydrolysis to peel off the coat. COP 1 Coated Vesicles bud from Golgi Apparatus. COP 2 Coated Vesicles bud from ER.

COPI and COPII Coated Vesicles
Sar1 is coat recruitment GTPase and is active when GTP is present and inactive when GDP is present. Sar1 insert tail into the membrane of ER. SNAREs function in the final event of docking of vesicles/containers with the target compartment and catalyze the fusion of the opposing membranes of the transport intermediate and the target compartment. Functionally, SNAREs can be classified into v-SNAREs that are associated with the vesicle/container and t-SNAREs that are associated with the target compartment. v-SNARE usually consists of a tail-anchored SNARE having a single SNARE motif, while a t-SNARE consists of either two or three polypeptides. COP II Coated Vesicles Carry Cargo from ER To Golgi. Only proteins that properly folded and assemble can leave the ER. Chaperon BiP bind with the misfolded protein and degrade it.

Protein Transport in Golgi Complex
Proteins having the KDEL (Lys-Asp-Gly-Leu) sequence return back to ER packed in COP1 coated vesicles. Golgi Apparatus consists of an ordered series of compartments. Gogli stacks has two distinct faces: Cis face (entry face), form Cis golgi network. Trans Face (exit face), form Tans golgi network. Lysosomes are membrane enclosed compartments used for intracellular digestion. They contain about 40 types of hydrolytic enzymes, including proteases, nucleases, glycosidases, lipases, phospholipases, phosphatases, and sulfatases. All are acid hydrolases. Transport proteins in this membrane allow the final products of the digestion of macromolecules such as amino acids, sugars, and nucleotides to be transported to the cytosol, from where they can be either excreted or reutilized by the cell. Endocytosed molecules are initially delivered in vesicles to small, irregularly shaped intracellular organelles called early endosomes. Some of these ingested molecules are selectively retrieved and recycled to the plasma membrane, while others pass on into late endosomes. Mature lysosomes form from the late endosomes, accompanied by a further decrease in internal pH. A second pathway to degradation in lysosomes is used in all cell types that is autophagy. Most of the lysosomal membrane proteins are unusually highly glycosylated, which helps to protect them from the lysosomal proteases in the lumen.

Protein Transport in Mitochondria
Protein translocation across mitochondrial membranes is mediated by multi-subunit protein complexes that function as protein translocators: the TOM complex functions across the outer membrane, and two TIM complexes, the TIM23 and TIM22 complexes, function across the inner membrane. The N-terminal signal sequence of the precursor protein is recognized by receptors of the TOM complex. The protein is thought to be translocated across both mitochondrial membranes at or near special contact sites. Directional transport requires energy. In most biological systems, energy is supplied by ATP hydrolysis. Mitochondrial protein import is fuelled by ATP hydrolysis at two discrete sites, one outside the mitochondria and one in the matrix. Bound cytosolic hsp70 is released from the protein in a step that depends on ATP hydrolysis. After initial insertion of the signal sequence and of adjacent portions of the polypeptide chain into the TOM complex, the signal sequence interacts with a TIM complex. The signal sequence is then translocated into the matrix in a process that requires an electrochemical H+ gradient across the inner membrane. Mitochondrial hsp70 thereby pull the protein into the matrix.

Hashmi, Uzair
  • Academics: MS
  • Specialization: Nanomedicine
  • Current: Researcher NUST, Entrepreneur 
  • University: NUST
  • Location: Islamabad, Pakistan
  •   
  • Course: Physiology
  • Clinical Years: 6
  • Teaching Years: 3

Uzair Hashmi secured his Bachelors in Applied Biosciences and Masters in Industrial Biotechnology with specialization in Nanomedicine from National University of Science and Technology (NUST)

Based on his bachelor's project he laid down the foundation of Pakistan's first disinfectant based startup Nanosmart and secured seed funding of 0.1 million. Startup got recognition in United nations Industrial development organization platform. 

He is the founder of Nano Smart-Small is the new Big (Disinfectants) and Feucher. He is very passionate about sharing knowledge. He believes in problem oriented research and has produced disinfectant solutions, nanobandages and hydrogels to tackle hospital acquired infections and to fasten the process of burn wound healing. 

Since 2014 he has taught over 4 diverse disciplines and also is a carrying out research in the fabrication of automated micro injector system for cellular injections

Furthermore, Uzair Hashmi is author of several publications published in international journals with good impact factor including Applied surface science, and journal of material chemistry.

31 lectures